The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Chemokine Expression in Melanoma Metastases Associated with CD8+ T-Cell Recruitment
Open accessPublished version of a preprint
Abstract
Despite the frequent detection of circulating tumor antigen-specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into metastatic tumor sites. Affymetrix gene expression profiling done on a series of metastatic melanoma biopsies revealed a major segregation of samples based on the presence or absence of T-cell-associated transcripts. The presence of lymphocytes correlated with the expression of defined chemokine genes. A subset of six chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) was confirmed by protein array and/or quantitative reverse transcription-PCR to be preferentially expressed in tumors that contained T cells. Corresponding chemokine receptors were found to be up-regulated on human CD8(+) effector T cells, and transwell migration assays confirmed the ability of each of these chemokines to promote migration of CD8(+) effector cells in vitro. Screening by chemokine protein array identified a subset of melanoma cell lines that produced a similar broad array of chemokines. These melanoma cells more effectively recruited human CD8(+) effector T cells when implanted as xenografts in nonobese diabetic/severe combined immunodeficient mice in vivo. Chemokine blockade with specific antibodies inhibited migration of CD8(+) T cells. Our results suggest that lack of critical chemokines in a subset of melanoma metastases may limit the migration of activated T cells, which in turn could limit the effectiveness of antitumor immunity.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Tumors from patients showing sustained treatment response predominately demonstrate a T cell-inflamed tumor microenvironment prior to, or early on, treatment.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [6]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“an effector population shown to be a target of downstream STING signaling involving the IFN-β-CXCL9/10 axis.54–58”
From Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation (2023) · cites this paper as [55]
Experimental — accuracy not yet measuredIn the citing paper
“Tumor analysis from patients with metastatic melanoma receiving vaccine and cytokine therapies suggested a paradigm of two broad phenotypes characterized by the presence or absence a T cell-inflamed tumor.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
Zlotnik, A., & Yoshie, O. (2000) · Immunity · doi:10.1016/s1074-7613(00)80165-x · Cited by 3,923 · cited 3×
“The indicated chemokines are GRO (1), IL-8 (2 ), CTACK (3), CXCL16 (4 ), IP-10 (5), MCP-1 (6), MIG (7), MIP-1a (8), MIP-1h (9), PARC (10), and RANTES (11 ).”
BackgroundCastellino, F., Huang, A. Y.-C., Altan-Bonnet, G. Y., Stoll, S., Scheinecker, C., & Germain, R. N. (2006) · Nature · doi:10.1038/nature04651 · Cited by 847 · cited 1×
“Recent work has suggested that CXCR4 and CCR5 may cooperatively provide a costimulatory signal for T-cell activation (16) and that CCR5 on CD8 T cells may be important for the generation of a memory phenotype (17).”
BackgroundSchadendorf, D., Ugurel, S., Schuler‐Thurner, B., Nestle, F. O., Enk, A., Bröcker, E.-B., Grabbe, S., Rittgen, W., Edler, L., Sucker, A., et al. (2006) · Annals of Oncology · doi:10.1093/annonc/mdj138 · Cited by 470 · cited 2×
“Three chemokine proteins that were reproducibly detected at abundant levels in the tumors with T cells were CCL2/MCP-1, CCL4/MIP-1h, and CCL5/RANTES.”
Rosenberg, S. A., Sherry, R. M., Morton, K. E., Sharfman, W., Yang, J. C., Topalian, S. L., Royal, R. E., Kammula, U. S., Restifo, N. P., Hughes, M. S., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.9.6169 · Cited by 460 · cited 2×
“Because it seemed likely that the protein array approach might not be sensitive enough to detect chemokines in low abundance, real-time RT-PCR was done for expression of CXCL9/Mig, CXCL10/IP-10, and CCL3/MIP-1a.”
Immune resistance orchestrated by the tumor microenvironment
Gajewski, T. F., Meng, Y., Blank, C., Brown, I., Kacha, A., Kline, J., & Harlin, H. (2006) · Immunological Reviews · doi:10.1111/j.1600-065x.2006.00442.x · Cited by 437 · cited 4×
“Numerous putative mechanisms by which tumors can evade immune attack despite the presence of antigen-specific CD8 effector T cells have been proposed and supported by preclinical models (7).”
BackgroundInfluentialRecent Advances in Chemokines and Chemokine Receptors
Zlotnik, A., Morales, J., & Hedrick, J. A. (1999) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v19.i1.10 · Cited by 410 · cited 1×
“and positively reinforce recruitment of additional specific T-cell subsets (13).”
BackgroundCancer vaccines based on the identification of genes encoding cancer regression antigens
Rosenberg, S. A. (1997) · Immunology Today · doi:10.1016/s0167-5699(97)84664-6 · Cited by 386 · cited 4×
“The indicated chemokines are GRO (1), IL-8 (2 ), CTACK (3), CXCL16 (4 ), IP-10 (5), MCP-1 (6), MIG (7), MIP-1a (8), MIP-1h (9), PARC (10), and RANTES (11 ).”
BackgroundInfluentialRosenberg, S. A., & Dudley, M. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405730101 · Cited by 366 · cited 1×
“Our results have implications for the use of autologous tumorinfiltrating lymphocytes (TIL) as an adoptive transfer immunotherapeutic strategy (23).”
ResultPriming of naive T cells inside tumors leads to eradication of established tumors
Yu, P., Lee, Y., Liu, W., Chin, R., Wang, J. H., Wang, Y., Schietinger, A., Philip, M., Schreiber, H. W., & Fu, Y. (2004) · Nature Immunology · doi:10.1038/ni1029 · Cited by 354 · cited 1×
“Transfection of tumor cells to express LIGHT results in potent tumor rejection (26), and introduction of an adenoviral vector encoding LIGHT can improve the control of preestablished tumors and promote rejection of micrometastases (27).”
Background
Cited by
Sorted by citations
Items 101–200 of 1,000
Enhancing cell therapies from the outside in: Cell surface engineering using synthetic nanomaterials
Stephan, M. T., & Irvine, D. J. (2011) · Nano Today · doi:10.1016/j.nantod.2011.04.001 · Cited by 270
Asrir, A., Tardiveau, C., Coudert, J., Laffont, R., Blanchard, L., Bellard, E., Veerman, K. M., Bettini, S., Lafouresse, F., Vina, E., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.01.002 · Cited by 286
Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma
Fankhauser, M., Broggi, M. A. S., Potin, L., Bordry, N., Jeanbart, L., Lund, A. W., Costa, E. M. D., Hauert, S., Rincón-Restrepo, M., Tremblay, C., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal4712 · Cited by 269
Baer, C., Squadrito, M. L., Laoui, D., Thompson, D., Hansen, S. K., Kiialainen, A., Hoves, S., Ries, C. H., Ooi, C.-H., & De Palma, M. (2016) · Nature Cell Biology · doi:10.1038/ncb3371 · Cited by 259
Noman, M. Z., Parpal, S., Van Moer, K., Xiao, M., Yu, Y., Arakelian, T., Viklund, J., De Milito, A., Hasmim, M., Andersson, M., et al. (2020) · Science Advances · doi:10.1126/sciadv.aax7881 · Cited by 255
Hoch, T., Schulz, D., Eling, N., Gómez, J. M. M., Levesque, M. P., & Bodenmiller, B. (2022) · Science Immunology · doi:10.1126/sciimmunol.abk1692 · Cited by 253
Gajewski, T. F., Louahed, J., & Brichard, V. G. (2010) · The Cancer Journal · doi:10.1097/ppo.0b013e3181eacbd8 · Cited by 250
Hong, M. L. W., Puaux, A., Huang, C. W., Loumagne, L., Tow, C., Mackay, C. R., Kato, M., Prévost‐Blondel, A., Avril, M., Nardin, A., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1466 · Cited by 262
Mechanisms of immune activation and regulation: lessons from melanoma
Kalaora, S., Nagler, A., Wargo, J. A., & Samuels, Y. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00442-9 · Cited by 252
Moreno Ayala, M. A., Campbell, T. F., Zhang, C., Dahan, N., Bockman, A., Prakash, V., Feng, L., Sher, T., & DuPage, M. (2023) · Immunity · doi:10.1016/j.immuni.2023.06.003 · Cited by 241
Zhang, P., Rashidi, A., Zhao, J., Silvers, C., Wang, H., Castro, B. A., Ellingwood, A., Han, Y., Lopez‐Rosas, A., Ζαννίκου, Μ., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37328-9 · Cited by 243
Chimeric antigen receptor T-cell therapy for solid tumors
Newick, K., Moon, E. K., & Albelda, S. Μ. (2016) · Molecular Therapy — Oncolytics · doi:10.1038/mto.2016.6 · Cited by 239
Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology
Jiao, X., Nawab, O., Patel, T. A., Kossenkov, A. V., Halama, N., Jaeger, D., & Pestell, R. G. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-1167 · Cited by 239
“As noted above, CCL5 promotes influx of CD8þ T cells (54) and PD-L1 expression is often associated with increased TILs.”
BackgroundMgrditchian, T., Arakelian, T., Paggetti, J., Noman, M. Z., Viry, E., Moussay, E., Van Moer, K., Kreis, S., Guerin, C., Buart, S., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1703921114 · Cited by 226
“While some reports highlight the role of CCL5 in promoting breast cancer metastasis (43), others refer the importance of CCL5 in T cell recruitment into melanomas (26).”
BackgroundImmune Cell Infiltration and Tertiary Lymphoid Structures as Determinants of Antitumor Immunity
Engelhard, V. H., Rodriguez, A. B., Mauldin, I. S., Woods, A. N., Peske, J. D., & Slingluff, C. L. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701269 · Cited by 231
Novel technologies and emerging biomarkers for personalized cancer immunotherapy
Yuan, J. D., Hegde, P. S., Clynes, R., Foukas, P. G., Harari, A., Kleen, T. O., Kvistborg, P., Maccalli, C., Maecker, H. T., Page, D. B., et al. (2016) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0107-3 · Cited by 235
Peng, W., Ye, Y., Rabinovich, B. A., Liu, C., Lou, Y., Zhang, M., Whittington, M., Yang, Y., Overwijk, W. W., Lizee, G. A., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0712 · Cited by 223
CAR T‐cell therapy of solid tumors
Yong, C. S. M., Dardalhon, V., Devaud, C., Taylor, N. N., Darcy, P. K., & Kershaw, M. H. (2016) · Immunology and Cell Biology · doi:10.1038/icb.2016.128 · Cited by 226
Wang, G., Zhang, Z., Zhong, K., Wang, Z., Nian, Y., Tang, X., Li, H., Lu, Q., Wu, Z., Yuan, B., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.08.021 · Cited by 230
“12 For instance, less than 1% of transferred CAR-T cells in fi ltrated fl ank tumors on the fi fth day in an NCG xenograft model.”
Immune Microenvironment in Tumor Progression: Characteristics and Challenges for Therapy
Chew, V., Toh, H. C., & Abastado, J. (2012) · Journal of Oncology · doi:10.1155/2012/608406 · Cited by 224
“Better understanding of the roles of immune cells and molecules in the tumor microenvironment will therefore be essential for the development of more effective novel treatments.”
BackgroundT-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy
Sackstein, R., Schatton, T., & Barthel, S. R. (2017) · Laboratory Investigation · doi:10.1038/labinvest.2017.25 · Cited by 220
Yang, L., Li, A., Lei, Q., & Zhang, Y. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0804-8 · Cited by 215
“It has been shown that a subset of melanoma patients with metastases exhibits a T cellinflamed tumor microenvironment as evidenced by gene expression profiling [9].”
BackgroundFong, L. H., Carroll, P. R., WEINBERG, V. K., Chan, S. E., Lewis, J., Corman, J. M., Amling, C. L., Stephenson, R. A., Simko, J. P., Sheikh, N. A., et al. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju268 · Cited by 215
Lymphatic vessels regulate immune microenvironments in human and murine melanoma
Lund, A. W., Wagner, M., Fankhauser, M., Steinskog, E. S. S., Broggi, M. A. S., Spranger, S., Gajewski, T. F., Alitalo, K. K., Eikesdal, H. P., Wiig, H., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci79434 · Cited by 218
“Furthermore, several immunotherapeutic strategies to treat metastatic melanoma appear to be dependent upon preexistence of an immune infiltrate (26, 27, 40).”
BackgroundThe Role of CXC Chemokine Receptors 1–4 on Immune Cells in the Tumor Microenvironment
Susek, K. H., Karvouni, M., Alici, E., & Lundqvist, A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02159 · Cited by 212
“effector T cells in a murine xenograft model (29)”
BackgroundWilliams, J. B., Horton, B. L., Zheng, Y., Duan, Y., Powell, J. D., & Gajewski, T. F. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20160485 · Cited by 213
“Spontaneously primed CD8+ T cells can home to tumor sites in mouse tumor models (Harlin et al., 2009; Fuertes et al., 2011) and in a subset of patients with advanced cancer (Harlin et al., 2006).”
BackgroundKim, H., Niu, L., Larson, P. G., Kucaba, T. A., Murphy, K. A., James, B. R., Ferguson, D. M., Griffith, T. S., & Panyam, J. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.02.034 · Cited by 213
Yu, J. W., Bhattacharya, S., Yanamandra, N., Kilian, D., Shi, H., Yadavilli, S., Katlinskaya, Y. V., Kaczynski, H., Conner, M., Benson, W., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0206223 · Cited by 204
Yang, M., Tao, L., Jiang, Y., Yang, J., Huo, Y., Liu, D., Li, J., Fu, X., He, R., Lin, C., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2689 · Cited by 208
“The spatial distribution of intratumoral CD8þ T cells is controlled by the following chemokines: CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10 (25, 26).”
BackgroundAdoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead
Kirtane, K., Elmariah, H., Chung, C. H., & Abate‐Daga, D. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-002723 · Cited by 205
“85 While these chemokine subsets may not be generalizable to all solid tumor malignancies, it suggests that critical chemokine receptor/ligand matches are necessary to allow for effector T-cell migration.”
BackgroundLu, X., Miao, L., Gao, W., Chen, Z., McHugh, K. J., Sun, Y., Tochka, Z. L., Tomasic, S. L., Sadtler, K., Hyacinthe, A., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz6606 · Cited by 200
Acquired and intrinsic resistance in cancer immunotherapy
Kelderman, S., Schumacher, T. N. M., & Haanen, J. B. A. G. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.07.011 · Cited by 197
Nakamura, T., Miyabe, H., Hyodo, M., Sato, Y., Hayakawa, Y., & Harashima, H. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.026 · Cited by 199
“Spontaneous immune responses against cancer are believed to contribute to the control of tumor growth in cancer patients, because the infiltration of preexisting T cells in tumor microenvironments appears to affect the prognostic benefit [1-3].”
BackgroundCorrales, L. P., & Gajewski, T. F. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1362 · Cited by 206
“Additional strategies to bring type I IFNs to the tumor microenvironment Because of the benefit of type I IFN induction in innate immune activation in the tumor microenvironment, alternative approaches also have been investigated to transform the tumor microenvironment favorably for T-cell–mediated regression.”
BackgroundInfluentialChen, X., Pan, X., Zhang, W., Guo, H., Cheng, S., He, Q., Yang, B., & Ding, L. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.09.006 · Cited by 203
Hendry, S. A., Farnsworth, R. H., Solomon, B., Achen, M. G., Stacker, S. A., & Fox, S. B. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00621 · Cited by 188
“Levels of chemokines within tumors, particularly the CXCR3 ligands CXCL9 and CXCL10, have been shown to correlate with T cell infiltration into tumors and enhanced antitumor responses (37, 38).”
BackgroundWennerberg, E., Kremer, V., Childs, R. W., & Lundqvist, A. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-014-1629-5 · Cited by 191
“These chemokines as well as CXCL11 (interferon-inducible T cell alpha chemoattractant, I-TAC) attract cells expressing the CXCR3 chemokine receptor [29], and secretion of CXCR3 ligands is associated with recruitment and infiltration of CXCR3-positive CTLs in several malignancies including renal cell carcinoma and mela…”
BackgroundVaccines targeting helper T cells for cancer immunotherapy
Melssen, M. M., & Slingluff, C. L. (2017) · Current Opinion in Immunology · doi:10.1016/j.coi.2017.07.004 · Cited by 201
Recent Developments in Cancer Vaccines
Palucka, K., Ueno, H., & Banchereau, J. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.0902539 · Cited by 193
“For example, the induced CD8 T cells might not migrate into the tumor lesions (15, 68), necessitating a better understanding of the trafficking into tumors of the elicited effector T cells.”
BackgroundArgyle, D. J., & Kitamura, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02629 · Cited by 195
CCL2: An Important Mediator Between Tumor Cells and Host Cells in Tumor Microenvironment
Jin, J., Lin, J., Xu, A., Lou, J., Qian, C., Li, X., Wang, Y., Yu, W., & Tao, H. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.722916 · Cited by 191
CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies
Knochelmann, H. M., Smith, A. S., Dwyer, C. J., Wyatt, M. M., Mehrotra, S., & Paulos, C. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01740 · Cited by 188
“enhancing Migration Tumors that express fewer chemokines often evade host surveillance via impairing effector T cell recruitment and infiltration into the tumor (61).”
BackgroundGordón‐Alonso, M., Hirsch, T., Wildmann, C., & van der Bruggen, P. (2017) · Nature Communications · doi:10.1038/s41467-017-00925-6 · Cited by 187
Which drug, and when, for patients with BRAF-mutant melanoma?
Jang, S., & Atkins, M. B. (2013) · The Lancet Oncology · doi:10.1016/s1470-2045(12)70539-9 · Cited by 182
Old dogs, new trick: classic cancer therapies activate cGAS
Yum, S., Li, M., & Chen, Z. J. (2020) · Cell Research · doi:10.1038/s41422-020-0346-1 · Cited by 184
Luke, J. J., Piha-Paul, S. A., Medina, T. M., Verschraegen, C. F., Varterasian, M. L., Brennan, A. M., Riese, R. J., Sokolovska, A., Strauss, J. F., Hava, D. L., et al. (2023) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-0118 · Cited by 188
Rodon, J. A., Argilés, G., Connolly, R. M., Vaishampayan, U. N., de Jonge, M. J. A., Garralda, E., Giannakis, M., Smith, D. C., Dobson, J. R., McLaughlin, M. E., et al. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01389-8 · Cited by 188
“These preliminary data showed an inverse association between the change in AXIN2 expression and the change in both a chemokine signature associated with T-cell recruitment (based on CCL2, CCL3, CCL4, CCL5, CXCL9, CXCL10) and an activated dendritic cell signature (based on BATF3, ITGAE, IRF8, CCR5, CCL3, CCL4, CXCL1).(…”
BackgroundWang-Bishop, L., Wehbe, M., Shae, D., James, J. L., Hacker, B. C., Garland, K. M., Chistov, P. P., Rafat, M., Balko, J. M., & Wilson, J. T. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000282 · Cited by 184
Wang, L., Amoozgar, Z., Huang, J., Saleh, M. H., Xing, D., Orsulic, S., & Goldberg, M. S. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0073 · Cited by 173
“Recent literature suggests that anti–CTLA-4 enhances CD8þ T-cell effector memory formation, function, and maintenance (49), which is consistent with our findings.”
BackgroundInfluentialMoon, E. K., Wang, L.-C. S., Bekdache, K., Lynn, R. C., Lo, A., Thorne, S. H., & Albelda, S. M. (2018) · OncoImmunology · doi:10.1080/2162402x.2017.1395997 · Cited by 174
“Unfortunately, there is often a chemokine/chemokine receptor “mismatch”, with tumors producing very small amounts of RANTES or CXCR3 ligands, thus resulting in inefficient targeting of CXCR3 high CD8 + effectors to tumor sites (14).”
BackgroundToward Precision Radiotherapy for Use with Immune Checkpoint Blockers
Vanpouille‐Box, C., Formenti, S. C., & Demaria, S. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0037 · Cited by 177
Reschke, R., Yu, J., Flood, B. A., Higgs, E. F., Hatogai, K., & Gajewski, T. F. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-003521 · Cited by 174
Genetic evolution of T-cell resistance in the course of melanoma progression
Sucker, A., Zhao, F., Real, B., Heeke, C., Bielefeld, N., Maβen, S., Horn, S., Moll, I., Maltaner, R., Horn, P. A., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0567 · Cited by 171
“Different mechanisms determine the migration of T cells into a metastatic lesion, such as the release of chemokines by tumor cells (45, 46).”
Yamada, N., Oizumi, S., Kikuchi, E., Shinagawa, N., Konishi-Sakakibara, J., 伊志嶺, 篤., Aoe, K., Gemba, K., Kishimoto, T., Torigoe, T., et al. (2010) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-010-0881-6 · Cited by 174
Trujillo, J. A., Luke, J. J., Zha, Y., Segal, J. P., Ritterhouse, L. L., Spranger, S., Matijevich, K., & Gajewski, T. F. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0780-0 · Cited by 159
Tumor matrix remodeling and novel immunotherapies: the promise of matrix-derived immune biomarkers
Mushtaq, M. U., Papadas, A., Pagenkopf, A. C., Flietner, E., Morrow, Z. T., Chaudhary, S. G., & Asimakopoulos, F. A. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0376-0 · Cited by 170
Dosta, P., Cryer, A. M., Dion, M. Z., Shiraishi, T., Langston, S., Lok, D. P. P., Wang, J., Harrison, S., Hatten, T., Ganno, M. L., et al. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01447-7 · Cited by 179
“49 ) and increased expression of chemokines IP-10, CXCL1 CCL3 and CCL2 in the TME, which are critical for antitumour T-cell activation and immune cell recruitment 50 .”
BackgroundBear, A. S., Kennedy, L. C., Young, J. K., Perna, S. K., Almeida, J. P. M., Lin, A. Y., Eckels, P. C., Drezek, R. A., & Foster, A. E. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069073 · Cited by 165
CXCL9: evidence and contradictions for its role in tumor progression
Ding, Q., Lu, P., Xia, Y., Ding, S., Fan, Y., Li, X., Han, P., Liu, J., Tian, D., & Liu, M. (2016) · Cancer Medicine · doi:10.1002/cam4.934 · Cited by 164
“found that in 44 biopsies of melanoma, highly expressed chemokines, including CXCL9, CCL2, CCL3, CCL4, CCL5, and CXCL10, correlated significantly with CD8+ T- cell recruitment and migration, which predicted good prognosis for cancer patients [61].”
BackgroundThe cGAS-STING Pathway: A Promising Immunotherapy Target
Ou, L., Zhang, A., Cheng, Y., & Chen, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.795048 · Cited by 166
Barriers to immune cell infiltration in tumors
Melssen, M. M., Sheybani, N., Leick, K. M., & Slingluff, C. L. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006401 · Cited by 173
Dendritic cells and immunity against cancer
Palucka, K., Ueno, H., Fay, J. W., & Banchereau, J. (2010) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02317.x · Cited by 164
Berghuis, D., Santos, S. J., Baelde, H. J., Taminiau, A. H. M., Egeler, R. M., Schilham, M. W., Hogendoorn, P. C. W., & Lankester, A. C. (2010) · The Journal of Pathology · doi:10.1002/path.2819 · Cited by 159
Control of CD8 T-Cell Infiltration into Tumors by Vasculature and Microenvironment
Peske, J. D., Woods, A. B., & Engelhard, V. H. (2015) · Advances in cancer research · doi:10.1016/bs.acr.2015.05.001 · Cited by 163
Chheda, Z. S., Sharma, R. K., Jala, V. R., Luster, A. D., & Haribabu, B. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502376 · Cited by 159
“T cells are present in higher numbers in tumors that express chemokines like CXCL9, CXCL10, CCL2, CCL3, CCL4 and CCL5 [162].”
Nanomedicine‐Boosting Tumor Immunogenicity for Enhanced Immunotherapy
Huang, J., Yang, B., Peng, Y., Huang, J., Wong, S. H. D., Bian, L., Zhu, K., Shuai, X., & Han, S. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202011171 · Cited by 160
Akalu, Y. T., Rothlin, C. V., & Ghosh, S. (2017) · Immunological Reviews · doi:10.1111/imr.12522 · Cited by 158
Role of Radiation Therapy in Modulation of the Tumor Stroma and Microenvironment
Menon, H., Ramapriyan, R., Cushman, T. R., Verma, V., Kim, H. H., Schoenhals, J. E., Atalar, S. C., Selek, U., Chun, S. G., Chang, J. Y., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00193 · Cited by 160
“(8) Depletion of resources and accumulation of tumor metabolic byproducts leads to blunting of CTL”
BackgroundInfluentialThe Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review
Zhang, J., & Wang, L. (2019) · Technology in Cancer Research & Treatment · doi:10.1177/1533033819831068 · Cited by 162
“There might also be an insufficient amount of chemokine receptors, such as CXC chemokine receptor type-3 (CXCR3), in tumor cells to attract T cells, and tumors may induce enhanced necrosis.(96,102,103) Fortunately, TCRs could be modified to improve T-cell trafficking and activation.”
BackgroundMoreno, B. H., Zaretsky, J. M., García-Díaz, Á., Tsoi, J., Parisi, G., Robert, L., Meeth, K. M., Ndoye, A., Bosenberg, M., Weeraratna, A. T., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0060 · Cited by 151
“This observation is consistent with other reports, where 568 chemokine-trafficking of immune cells into tumors was observed 569 in humanmelanoma cell lines (49) or in mice receiving adoptive 570 cell therapy and anti–PD-1 blockade (50).”
ResultCytokine and Chemokine Signals of T‐Cell Exclusion in Tumors
Zhang, Y., Guan, X.-Y., & Jiang, P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.594609 · Cited by 133
Oldford, S. A., Haidl, I. D., Howatt, M., Leiva, C., Johnston, B., & Marshall, J. S. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001137 · Cited by 148
“We have demonstrated that TLR2-activated mast cells secrete large amounts of CCL3, which has been demonstrated to be chemotactic for mature NK cells (35) and activated CD8 T cells (36, 37).”
BackgroundAllen, F., Bobanga, I., Rauhe, P., Barkauskas, D. S., Teich, N., Tong, C., Myers, J., & Huang, A. Y.-C. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1393598 · Cited by 150
“Although T cells constitute another major source of IFNg in the tumor rejection process, our data is further supported by previous studies using IFNg-deficient T cells to demonstrate that NK cells could supply much of the IFNg needed in effective tumor rejection.16 However, NK cells also are dependent on T cells for f…”
BackgroundResultInfluentialAung, A., Kumar, V., Theprungsirikul, J., Davey, S. K., & Varghese, S. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-0342 · Cited by 146
Romero, J. M., Grünwald, B., Jang, G.-H., Bavi, P. P., Jhaveri, A., Masoomian, M., Fischer, S. E., Zhang, A., Denroche, R. E., Lungu, I. M., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2803 · Cited by 146
Tumor-intrinsic oncogene pathways mediating immune avoidance
Spranger, S., & Gajewski, T. F. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1086862 · Cited by 154
Mugarza, E., van Maldegem, F., Boumelha, J., Moore, C., Rana, S., Llorian, M., East, P., Ambler, R., Anastasiou, P., Romero-Clavijo, P., et al. (2022) · Science Advances · doi:10.1126/sciadv.abm8780 · Cited by 153
Bergamaschi, C., Pandit, H., Nagy, B. A., Stellas, D., Jensen, S. M., Bear, J., Cam, M. C., Valentin, A., Fox, B. A., Felber, B. K., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000599 · Cited by 141
Engineering-enhanced CAR T cells for improved cancer therapy
Milone, M. C., Xu, J., Chen, S., Collins, M. A., Zhou, J., Powell, D. J., & Melenhorst, J. J. (2021) · Nature Cancer · doi:10.1038/s43018-021-00241-5 · Cited by 148
Park, H.-H., Kim, H.-R., Park, S.-Y., Hwang, S., Hong, S. M., Park, S., Kang, H. C., Morgan, M. J., Cha, J., Lee, D., et al. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01399-3 · Cited by 141
“Indeed, the activation of RIPK1/RIPK3 leads to the upregulation of inflammatory chemokines that promote the cross-priming of CD8 T cell vaccination responses [11–13]; the presence of intratumoral chemokines is positively correlated with cytotoxic CD8 T cell (CTL) infiltration [14] indicating that the activation of nec…”
BackgroundEnhancement of T cell recruitment and infiltration into tumours
Oelkrug, C., & Ramage, J. M. (2014) · Clinical & Experimental Immunology · doi:10.1111/cei.12382 · Cited by 143
Radiation therapy-induced remodeling of the tumor immune microenvironment
Charpentier, M., Spada, S., Nest, S. J. V., & Demaria, S. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.04.003 · Cited by 149
Oncogenic CXCL10 signalling drives metastasis development and poor clinical outcome
Wightman, S. C., Uppal, A., Pitroda, S. P., Ganai, S., Burnette, B., Stack, M. E., Oshima, G., Khan, S. A., Huang, X., Posner, M. C., et al. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.193 · Cited by 137
“The CXCL10 produced by tumour or host cells can recruit CXCR3þ tumour-infiltrating T cells and NK cells associated with tumour suppression (Luster and Leder, 1993; Wenzel et al, 2005; Fujita et al, 2009; Harlin et al, 2009; Dengel et al, 2010; Antonicelli et al, 2011; Wennerberg et al, 2014).”
BackgroundMolecular profiling to identify relevant immune resistance mechanisms in the tumor microenvironment
Gajewski, T. F., Fuertes, M. B., Spaapen, R. M., Zheng, Y., & Kline, J. P. (2010) · Current Opinion in Immunology · doi:10.1016/j.coi.2010.11.013 · Cited by 138
“Using a transwell system in vitro, each of these chemokines was sufficient to recruit CD8+ effector T cells, suggesting some redundancy [5].”
BackgroundMethodInfluentialMulligan, A. M., Raitman, I., Feeley, L., Pinnaduwage, D., Nguyen, L. T., O’Malley, F. P., Ohashi, P. S., & Andrulis, I. L. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3314 · Cited by 143
“For example, CXCL10 expression was only found in hepatocellular carcinomas in which there was marked lymphocyte infiltration (4), and CXCL10 expression in melanoma metastases was found to be associated with CD8þ T lymphocyte recruitment (35).”
BackgroundSupercharging adoptive T cell therapy to overcome solid tumor–induced immunosuppression
Mardiana, S., Solomon, B., Darcy, P. K., & Beavis, P. A. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw2293 · Cited by 140
STING, DCs and the link between innate and adaptive tumor immunity
Vatner, R. E., & Janssen, E. M. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.12.001 · Cited by 139
“In human patients with metastatic melanoma, metastatic lesions infiltrated with T cells are characterized by an IFN gene signature (Fuertes et al., 2011; Harlin et al., 2009) .”
BackgroundDendritic Cells, the T-cell-inflamed Tumor Microenvironment, and Immunotherapy Treatment Response
Garris, C., & Luke, J. J. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1321 · Cited by 146
“Gene expression analysis of metastatic melanoma lesions identified a strong separation of samples based on T-cell-associated gene transcripts (6).”
BackgroundLayer, J. P., Kronmüller, M., Quast, T., Konijnenberg, D., Effern, M., Hinze, D., Althoff, K., Schramm, A. R., Westermann, F., Peifer, M., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1320626 · Cited by 138
HDAC inhibitors enhance the immunotherapy response of melanoma cells
Booth, L. A., Roberts, J. L., Poklepovic, A. S., Kirkwood, J. M., & Dent, P. (2017) · Oncotarget · doi:10.18632/oncotarget.17950 · Cited by 136
Bommareddy, P. K., Zloza, A., Rabkin, S. D., & Kaufman, H. L. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1591875 · Cited by 143
“While cGAS-STING signaling explains the presence of tumor-infiltrating T cells, this pathway also enhances expression of several counter-regulatory immune parameters, including expression of PD-1 ligand 1 (PD-L1), accumulation of CD4FoxP3 regulatory T cells, and production of indoleamine 2,3-dioxygenase (IDO), all fac…”
BackgroundYoshikawa, T., Wu, Z., Inoue, S., Kasuya, H., Matsushita, H., Takahashi, Y., Kuroda, H., Hosoda, W., Suzuki, S., & Kagoya, Y. (2021) · Blood · doi:10.1182/blood.2021012714 · Cited by 134
Immunogenomic Classification of Colorectal Cancer and Therapeutic Implications
Roelands, J. P., Kuppen, P. J. K., Vermeulen, L., Maccalli, C., Decock, J. V., Wang, E., Marincola, F. M., Bedognetti, D., & Hendrickx, W. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102229 · Cited by 136
Chimeric-antigen receptor T (CAR-T) cell therapy for solid tumors: challenges and opportunities
Xia, A., Wang, X., Lu, Y., Lu, X., & Sun, B. (2017) · Oncotarget · doi:10.18632/oncotarget.19361 · Cited by 132
“Furthermore, owing to the mismatch between chemokine receptors expression on T cells and tumor chemokine signature, T lymphocytes can hardly migrate into the tumor, and thus lose the immune function against cancer [42].”
BackgroundCAR-T Cell Therapy for Breast Cancer: From Basic Research to Clinical Application
Yang, Y.-H., Liu, J., Lu, C., & Wei, J. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.70120 · Cited by 135
“Unfortunately, the mismatches between chemokine receptors on T cells and chemokines on tumor cells were frequently reported[171].”
BackgroundInnate immune mediators in cancer: between defense and resistance
Berraondo, P., Minute, L., Ajona, D., Corrales, L. P., Melero, I., & Pı́o, R. (2016) · Immunological Reviews · doi:10.1111/imr.12464 · Cited by 134
Toll-Like Receptor 9 Agonists in Cancer
Karapetyan, L., Luke, J. J., & Davar, D. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s247050 · Cited by 138
Interferons and the immunogenic effects of cancer therapy
Minn, A. J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.09.007 · Cited by 130
“These ISGs often reflect the activation of T cells and an “inflamed tumor microenvironment” [34] that Minn Page 5”
BackgroundHyperprogression under Immunotherapy
Frélaut, M., Tourneau, C. L., & Borcoman, É. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112674 · Cited by 130
Chibaya, L., Murphy, K. C., DeMarco, K. D., Gopalan, S., Liu, H., Parikh, C. N., Lopez-Diaz, Y., Faulkner, M., Li, J., Morris, J. P., et al. (2023) · Nature Cancer · doi:10.1038/s43018-023-00553-8 · Cited by 138
Metadata
- Authors
- Harlin, H., Meng, Y., Peterson, A. C., Zha, Y., Tretiakova, M., Slingluff, C., McKee, M., & Gajewski, T. F.
- Affiliations
- 1Department of Pathology,
- 2Department of Medicine, Section of Hematology/Oncology, and
- University of Virginia (US)
- University of Chicago (US)
- Venue
- Cancer Research
- Published
- 2009-04-01
- Volume
- 69
- Issue
- 7
- Pages
- 3077-3085
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3886718
- OpenAlex
- W2162222767
- Cited by
- 1,121
- References
- 29
- Citations by year
- 2026: 40 · 2025: 58 · 2024: 89 · 2023: 95 · 2022: 118 · 2021: 121 · 2020: 105 · 2019: 87 · 2018: 69 · 2017: 77 · 2016: 51 · 2015: 42 · 2014: 29 · 2013: 37 · 2012: 28
- FWCI
- 17.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Burroughs Wellcome Fund
- University of Chicago
- National Cancer Institute (P01CA97296, R01 CA90575, R01CA090575, P01CA097296, P30CA044579)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- melanoma metastasis, chemokines, CD8+ T cell recruitment, T cell migration, MCP-1, CCL3, carbon tetrachloride, RANTES, CXCL9, CXCL10, chemokine receptors, tumor immune microenvironment, chemokine blockade, antitumor immunity, melanoma cell lines, xenografts
- MeSH terms
- Cell Movement, Multigene Family, Humans, Melanoma, Gene Expression, CD8-Positive T-Lymphocytes, Chemokines, Protein Array Analysis, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
