The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.
Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy
Open accessAbstract
Preventing trafficking of myeloid-derived suppressor cells to the tumor site enhances the efficiency of checkpoint blockade.
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?
In the citing paper
“Notably, data from various mouse models indicate that disrupting the CXCR1/2–MDSC axis in tumours is therapeutically efficacious across a wide variety of solid cancers166–172.”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [168]
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
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Safety, activity, and immune correlates of anti–PD-1 antibody in cancer
Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., Powderly, J. D., Carvajal, R. D., Sosman, J. A., Atkins, M. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200690 · Cited by 12,628
Safety and activity of anti-PD-L1 antibody in patients with advanced cancer
Brahmer, J. R., Tykodi, S. S., Chow, L. Q. M., Hwu, W.-J., Topalian, S. L., Hwu, P., Drake, C. G., Camacho, L. H., Kauh, J., Odunsi, K., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1200694 · Cited by 7,945
Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294 · cited 1×
“Signaling of PD1 on T cells via PD-L1 (B7-H1) or PD-L2 (B7-DC) inhibits T cell receptor–mediated activation by recruitment of the SHP2 phosphatase (2).”
BackgroundTumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Robert, C., Thomas, L., Bondarenko, I., O'Day, S., Weber, J., Garbe, C., Lebbe, C., Baurain, J.-F., Testori, A., Grob, J.-J., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1104621 · Cited by 4,496
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230 · cited 1×
“Combination regimens appear to be even more potent with response rates of 53% in metastatic melanoma (22).”
BackgroundCoordinated regulation of myeloid cells by tumours
Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012) · Nature Reviews Immunology · doi:10.1038/nri3175 · Cited by 3,544 · cited 2×
“These results are consistent with previous reports demonstrating that GrMDSCs at the tumor site are highly dependent on migration from the BM or spleen and undergo minimal proliferation within the tumor bed (13).”
BackgroundResultIwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192461099 · Cited by 3,261
Cited by
Sorted by citations
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy
Sharma, P., Hu-Lieskovan, S., Wargo, J. A., & Ribas, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.017 · Cited by 5,588
“For example, tumors secrete ligands CCL5, CCL7, and CXCL8, bind to their receptors CCR1 or CXCR2 expressed on subtypes of MDSCs (Highfill et al., 2014), and attract MDSCs in the tumor microenvironment.”
Inflammation and tumor progression: signaling pathways and targeted intervention
Zhao, H., Wu, L., Yan, G., Chen, Y., Zhou, M., Wu, Y., & Li, Y. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00658-5 · Cited by 3,058
Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity
Veglia, F., Sanseviero, E., & Gabrilovich, D. I. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-00490-y · Cited by 1,940
Neutrophils in cancer: Neutral no more
Coffelt, S. B., Wellenstein, M. D., & de Visser, K. E. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.52 · Cited by 1,830
Myeloid-Derived Suppressor Cells
Gabrilovich, D. I. (2017) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0297 · Cited by 1,935
“The level of MDSCs is associated with patient responses to CTLA-4/ipilimumab (58, 59) and PD-1 (60, 61) inhibition.”
BackgroundTumor microenvironment and therapeutic response
Wu, T., & Dai, Y. (2017) · Cancer Letters · doi:10.1016/j.canlet.2016.01.043 · Cited by 1,802
Myeloid-derived suppressor cells coming of age
Veglia, F., Perego, M., & Gabrilovich, D. I. (2018) · Nature Immunology · doi:10.1038/s41590-017-0022-x · Cited by 1,818
Lei, X., Lei, Y., Li, J.-K., Du, W.-X., Li, R.-G., Yang, J., Li, J., Li, F., & Tan, H.-B. (2020) · Cancer Letters · doi:10.1016/j.canlet.2019.11.009 · Cited by 1,470
Mechanisms of resistance to immune checkpoint inhibitors
Jenkins, R. W., Barbie, D. A., & Flaherty, K. T. (2018) · British Journal of Cancer · doi:10.1038/bjc.2017.434 · Cited by 1,383
“Depletion of these immune suppressive cell types (e.g., MDSCs and Tregs) has experimentally been shown to enhance anti-tumour immune responses overcoming innate resistance (Highfill et al, 2014; Ngiow et al, 2015).”
BackgroundTargeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy
Jiang, H., Hegde, S., Knolhoff, B. L., Zhu, Y., Herndon, J. M., Meyer, M. A., Nywening, T. M., Hawkins, W. G., Shapiro, I. M., Weaver, D. T., et al. (2016) · Nature Medicine · doi:10.1038/nm.4123 · Cited by 1,060
Tumour-associated neutrophils in patients with cancer
Shaul, M. E., & Fridlender, Z. G. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0222-4 · Cited by 1,067
Immune Escape Mechanisms as a Guide for Cancer Immunotherapy
Beatty, G. L., & Gladney, W. L. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1860 · Cited by 1,078
“In support of this approach, Highfill and colleagues recently demonstrated a role for inhibiting the trafficking of myeloid suppressor cells into tumors by disruption of CXCR2 signaling as a strategy for unveiling the antitumor activity of anti–PD-1 therapy (34).”
BackgroundOvercoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells
Henau, O. D., Rausch, M. P., Winkler, D. A., Campesato, L. F., Liu, C., Hirschhorn-Cymerman, D., Budhu, S., Ghosh, A., Pink, M. M., Tchaicha, J. H., et al. (2016) · Nature · doi:10.1038/nature20554 · Cited by 862
Steele, C. W., Karim, S. A., Leach, J. D. G., Bailey, P. J., Upstill‐Goddard, R., Rishi, L., Foth, M., Bryson, S., McDaid, K., Wilson, Z., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.04.014 · Cited by 857
“CXCR2 also regulates the migration of myeloid-derived suppressor cells (MDSCs) (Highfill et al., 2014).”
Teijeira, Á., Garasa, S., Gato, M., Alfaro, C., Miguéliz, I., Cirella, A., de Andrea, C., Ochoa, M. C., Otano, I., Etxeberría, I., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.03.001 · Cited by 826
Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases
Ha, H., Debnath, B., & Neamati, N. (2017) · Theranostics · doi:10.7150/thno.15625 · Cited by 805
“Inhibition of programmed death-1 (PD-1) by anti-PD-1 antibody prevented tumor growth during early phase tumor progression, but delayed treatment with anti-PD-1 therapy showed little benefits [346].”
InfluentialGenetics and biology of prostate cancerPreprint
Wang, G., Zhao, D., Spring, D. J., & DePinho, R. A. (2018) · Genes & Development · doi:10.1101/gad.315739.118 · Cited by 814
Fares, C. M., Allen, E. M. V., Drake, C. G., Allison, J. P., & Hu‐Lieskovan, S. (2019) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_240837 · Cited by 665
Emran, T. B., Shahriar, A., Mahmud, A. R., Rahman, T., Abir, M. H., Siddiquee, M. F. R., Ahmed, H., Rahman, N., Nainu, F., Wahyudin, E., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.891652 · Cited by 606
Cambier, S., Gouwy, M., & Proost, P. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-00974-6 · Cited by 605
“Moreover, CXCL8 induced the release of NETs in granulocytic MDSCs in vitro [108, 109].”
BackgroundTumor microenvironment participates in metastasis of pancreatic cancer
Ren, B., Cui, M., Yang, G., Wang, H., Feng, M., You, L., & Zhao, Y. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0858-1 · Cited by 597
Resistance to PD1/PDL1 checkpoint inhibition
O’Donnell, J. S., Long, G. V., Scolyer, R. A., Teng, M. W. L., & Smyth, M. J. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.11.007 · Cited by 587
The current state of the art and future trends in RAS-targeted cancer therapies
Punekar, S. R., Velcheti, V., Neel, B. G., & Wong, K.-K. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00671-9 · Cited by 549
Alshetaiwi, H. S., Pervolarakis, N., McIntyre, L. L., Ma, D., Nguyen, Q., Rath, J. A., Nee, K., Hernandez, G. A., Evans, K. T., Torosian, L., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.aay6017 · Cited by 532
Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine
Campesato, L. F., Budhu, S., Tchaicha, J. H., Weng, C., Gigoux, M., Cohen, I., Redmond, D., Mangarin, L. M. B., Pourpe, S., Liu, C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17750-z · Cited by 549
Mira, J. C., Gentile, L. F., Mathias, B. J., Efron, P. A., Brakenridge, S. C., Mohr, A. M., Moore, F. A., & Moldawer, L. L. (2017) · Critical Care Medicine · doi:10.1097/ccm.0000000000002074 · Cited by 526
“Additionally, blockade of C-X-C motif chemokine receptor 2-mediated MDSC trafficking has been shown to enhance anti-programmed death 1 signaling efficacy in a murine model (79).”
BackgroundGenetically engineered mouse models in oncology research and cancer medicine
Kersten, K., de Visser, K. E., van Miltenburg, M. H., & Jonkers, J. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201606857 · Cited by 502
“…that boosting dendritic cell function (Broz et al , 2014; Ruffell et al , 2014; Salmon et al , 2016; Sa ´ nchez-Paulete et al , 2016) or blocking myeloid cell-induced immunosuppression (Highfill et al , 2014; Zhu et al , 2014) improves the anti-tumor efficacy of immune checkpoint blockade.”
Nywening, T. M., Belt, B. A., Cullinan, D. R., Panni, R. Z., Han, B. J., Sanford, D. E., Jacobs, R. C., Ye, J., Patel, A. A., Gillanders, W. E., et al. (2017) · Gut · doi:10.1136/gutjnl-2017-313738 · Cited by 506
Big opportunities for small molecules in immuno-oncology
Adams, J. L., Smothers, J. F., Srinivasan, R., & Hoos, A. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4596 · Cited by 492
Chiu, D. K.-C., Tse, A. P.-W., Xu, I. M.-J., Di Cui, J., Lai, R. K.-H., Li, L. L., Koh, H.-Y., Tsang, F. H.-C., Wei, L. L., Wong, C.-M., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00530-7 · Cited by 448
Classification of current anticancer immunotherapies
Galluzzi, L., Vacchelli, E., Pedro, J. M. B., Buqué, A., Senovilla, L., Baracco, E. E., Bloy, N., Castoldi, F., Abastado, J., Agostinis, P., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.2998 · Cited by 481
“These include: (1) strategies for the depletion of circulating myeloid-derived suppressor cells (MDSCs), a bloodborne population of immature, immunosuppressive myeloid cells that generally accumulate in the course of tumor progression [513-516]; (2) mAbs that block CD47, one of the major antiphagocytic receptor expres…”
BackgroundMyeloid-derived suppressor cells: an emerging target for anticancer immunotherapy
Wu, Y., Yi, M., Niu, M., Mei, Q., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01657-y · Cited by 475
“Inhibition of CXCR2 has been shown to rescue MDSCs trafficking and enhance anti-PD-1 efficacy in murine glioblastoma and rhabdomyosarcoma [196, 197].”
BackgroundNeutrophils in cancer: prognostic role and therapeutic strategies
Ocaña, A., Nieto‐Jiménez, C., Pandiella, A., & Templeton, A. J. (2017) · Molecular Cancer · doi:10.1186/s12943-017-0707-7 · Cited by 470
“Some studies have suggested an augmented effect when neutrophil targeting agents, CXCR2 inhibitors or anti-Ly6G, were combined with checkpoint inhibitors [46, 47].”
BackgroundMyeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer
Law, A. M. K., Valdes-Mora, F., & Gallego-Ortega, D. (2020) · Cells · doi:10.3390/cells9030561 · Cited by 455
Zhang, Y., Chandra, V., Riquelme, E. M., Dutta, P., Quesada, P. R., Rakoski, A. I., Zoltan, M. A., Arora, N., Baydogan, S., Horne, W. T., et al. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190354 · Cited by 451
Resistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors
Lei, Q., Wang, D., Sun, K., Wang, L., & Zhang, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00672 · Cited by 431
Lin, C., He, H., Liu, H., Li, R., Chen, Y., Qi, Y., Jiang, Q., Chen, L., Zhang, P., Zhang, H., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-316324 · Cited by 420
Self-citationAlfaro, C., Teijeira, A., Oñate, C., Pérez, G., Sanmamed, M. F., Andueza, M. P., Alignani, D., Labiano, S., Azpilikueta, A., Rodriguez-Paulete, A., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2463 · Cited by 417
“However, our results further argue in favor of the convenience of pharmacologically inhibiting IL-8 as previously carried out in xenografted mouse models and currently in clinical trials with neutralizing antibodies (51) and small drug inhibitors (52).”
ResultImmunosuppressive cells in tumor immune escape and metastasis
Liu, Y., & Cao, X. (2015) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1376-x · Cited by 410
Mechanisms of Resistance to PD-1 and PD-L1 Blockade
Nowicki, T. S., Hu‐Lieskovan, S., & Ribas, A. (2018) · The Cancer Journal · doi:10.1097/ppo.0000000000000303 · Cited by 408
“Several studies have demonstrated that depletion of intratumorMDSCs restores the effectiveness of PD-1 blockade.(78,79) Another immunosuppressive cell type within the TME is the regulatory T (Treg) cell.”
Lessons learned from the blockade of immune checkpoints in cancer immunotherapy
Li, X., Shao, C., Shi, Y., & Han, W. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0578-4 · Cited by 389
“Growing evidence also suggest that heavy tumor infiltration by MDSCs correlated with poor prognosis and decreased efficacy of immunotherapies, including ICB therapy [74], adoptive T cell therapy (ACT) [75], and DCs vaccines [76].”
BackgroundChemokines Modulate Immune Surveillance in Tumorigenesis, Metastasis, and Response to Immunotherapy
Vilgelm, A. E., & Richmond, A. J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00333 · Cited by 378
Interleukin-8 in cancer pathogenesis, treatment and follow-up
Alfaro, C., Sanmamed, M. F., Rodriguez-Ruiz, M. E., Teijeira, Á., Oñate, C., González, Á., Ponz‐Sarvisé, M., Schalper, K. A., Perez‐Gracia, J. L., & Melero, I. (2017) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2017.08.004 · Cited by 380
Loeuillard, E. J., Yang, J., Buckarma, E. H., Wang, J., Liu, Y., Conboy, C. B., Pavelko, K. D., Li, Y., O’Brien, D. R., Wang, C., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137110 · Cited by 376
“MDSCs also have a significant association with poor patient outcomes as well as chemotherapy and immunotherapy resistance (35, 47).”
BackgroundTargeting cancer-promoting inflammation — have anti-inflammatory therapies come of age?
Hou, J., Karin, M., & Sun, B. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-00459-9 · Cited by 387
Immunosuppression associated with chronic inflammation in the tumor microenvironment
Wang, D., & DuBois, R. N. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv123 · Cited by 368
“However, recent in vivo studies showed that inhibition of tumor-infiltrating MDSCs by targeting CXCR2 enhanced antiPD-1 efficacy in rhabdomyosarcoma in vivo (125) and improved the efficacy of chemotherapy in a spontaneous mouse model of prostate cancer (71).”
BackgroundTumor Immune Microenvironment during Epithelial–Mesenchymal Transition
Taki, M., Abiko, K., Ukita, M., Murakami, R., Yamanoi, K., Yamaguchi, K. D., Hamanishi, J., Baba, T., Matsumura, N., & Mandai, M. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4459 · Cited by 368
Potential roles and targeted therapy of the CXCLs/CXCR2 axis in cancer and inflammatory diseases
Cheng, Y., Ma, X., Wei, Y.-Q., & Wei, X. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.01.005 · Cited by 352
Neutrophil phenotypes and functions in cancer: A consensus statement
Quail, D. F., Amulic, B., Aziz, M., Barnes, B. J., Eruslanov, E. B., Fridlender, Z. G., Goodridge, H. S., Granot, Z., Hidalgo, A., Huttenlocher, A., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220011 · Cited by 347
“In preclinical models of childhood cancers such as rhabdomyosarcoma, CXCR2+Ly6G+ cells mediate local immunosuppression, while CXCR2 inhibition improves immune checkpoint blockade efficacy (Highfill et al., 2014).”
BackgroundAdrover, J. M., McDowell, S. A. C., He, X., Quail, D. F., & Egeblad, M. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.001 · Cited by 365
Tumor microenvironment in gastric cancers
Oya, Y., Hayakawa, Y., & Koike, K. (2020) · Cancer Science · doi:10.1111/cas.14521 · Cited by 338
Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors
Merchant, M. S., Wright, M., Baird, K., Wexler, L. H., Rodriguez-Galindo, C., Bernstein, D., Delbrook, C., Lodish, M., Bishop, R., Wolchok, J. D., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0491 · Cited by 331
“, MDSC, Treg) so that effective immune checkpoint therapy may require combination therapies for maximal impact (25, 32).”
BackgroundSelf-citationEpigenetic therapy inhibits metastases by disrupting premetastatic niches
Lu, Z., Zou, J., Li, S., Topper, M. J., Tao, Y., Zhang, H., Jiao, X., Xie, W., Kong, X., Vaz, M., et al. (2020) · Nature · doi:10.1038/s41586-020-2054-x · Cited by 330
Self-citationReduction of MDSCs with all-trans retinoic acid improves CAR therapy efficacy for sarcomas
Long, A. H., Highfill, S. L., Cui, Y., Smith, J. P., Walker, A. J., Ramakrishna, S., El-Etriby, R., Galli, S., Tsokos, M. G., Orentas, R. J., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0230 · Cited by 329
“Granulocytic MDSCs are a primary mediator of immune evasion in murine models of sarcoma (30), so we examined whether similar MDSCs were contributing to an immunosuppressive microenvironment that inhibits in vivo efficacy of GD2-CAR T cells against sarcomas.”
BackgroundInfluentialSelf-citationEmerging Opportunities and Challenges in Cancer Immunotherapy
Whiteside, T. L., Demaria, S., Rodriguez-Ruiz, M. E., Zarour, H. M., & Melero, I. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0049 · Cited by 325
“Not surprisingly, MDSC accumulation in tumors appears to interfere with anti–PD-1 immunotherapy, and targeting of CXCR2þ MDSC with antibodies was reported to improve the efficiency of the checkpoint blockade (44).”
BackgroundThe Role of Tumor-Associated Neutrophils in Colorectal Cancer
Mizuno, R., Kawada, K., Itatani, Y., Ogawa, R., Kiyasu, Y., & Sakai, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030529 · Cited by 316
Ren, D., Hua, Y., Yu, B., Ye, X., He, Z., Li, C., Wang, J., Mo, Y., Wei, X., Chen, Y., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-1144-6 · Cited by 320
“In children with metastatic sarcoma, the efficacy of PD-1 blockade therapy was significantly improved by treatment with an anti-CXCR2 monoclonal antibody [168].”
BackgroundTumor-associated neutrophils and neutrophil-targeted cancer therapies
Que, H., Fu, Q., Lan, T., Tian, X., & Wei, X. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188762 · Cited by 324
Improving head and neck cancer therapies by immunomodulation of the tumour microenvironment
Ruffin, A. T., Li, H., Vujanovic, L. N., Zandberg, D. P., Ferris, R. L., & Bruno, T. C. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00531-9 · Cited by 326
Human neutrophils: Their role in cancer and relation to myeloid-derived suppressor cells
Moses, K., & Brandau, S. (2016) · Seminars in Immunology · doi:10.1016/j.smim.2016.03.018 · Cited by 306
Therapeutic targeting of tumour myeloid cells
Barry, S. T., Gabrilovich, D. I., Sansom, O. J., Campbell, A. D., & Morton, J. P. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00546-2 · Cited by 305
Beatty, G. L., Winograd, R., Evans, R. A., Long, K. B., Luque, S. L., Lee, J. W., Clendenin, C., Gladney, W. L., Knoblock, D. M., Guirnalda, P. D., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.04.010 · Cited by 297
Horvath, L., Thienpont, B., Zhao, L., Wolf, D. G. F., & Pircher, A. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01260-z · Cited by 288
Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity
Ring, N. G., Herndler‐Brandstetter, D., Weiskopf, K., Shan, L., Volkmer, J.-P., George, B. M., Lietzenmayer, M., McKenna, K. M., Naik, T. J., McCarty, A., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710877114 · Cited by 288
Shi, L., Wang, J., Ding, N., Zhang, Y., Zhu, Y., Dong, S., Wang, X., Peng, C., Zhou, C., Zhou, L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13204-3 · Cited by 290
Zhang, H., Ye, Y. L., Li, M.-X., Ye, S.-B., Huang, W.-R., Cai, T.-T., He, J., Peng, J.-Y., Duan, T., Cui, J., et al. (2016) · Oncogene · doi:10.1038/onc.2016.367 · Cited by 279
Self-citationBao, Y., Zhai, J., Chen, H., Wong, C. C., Liang, C., Ding, Y., Huang, D., Gou, H., Chen, D., Pan, Y., et al. (2023) · Gut · doi:10.1136/gutjnl-2022-328845 · Cited by 282
“Considering that reduced infiltration of MDSCs has been reported to correlate with enhanced immunotherapeutic efficacy in various cancer types, 22 29 30 we sought to test if targeting YTHDF1 augments anti-PD1 therapy in CRC.”
Bilušić, M., Heery, C. R., Collins, J. M., Donahue, R. N., Palena, C., Madan, R. A., Karzai, F. H., Marté, J. L., Strauss, J., Gatti-Mays, M. E., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0706-x · Cited by 274
IL8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy
Teijeira, Á., Garasa, S., Ochoa, M. C., Villalba-Esparza, M., Olivera, I., Cirella, A., Eguren‐Santamaría, I., Berraondo, P., Schalper, K. A., de Andrea, C. E., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-1319 · Cited by 275
“11), and neutrophils, withmajor implications for antitumor immunity (12).”
BackgroundConche, C., Finkelmeier, F., Pesic, M. H., Nicolas, A. M., Böttger, T. W., Kennel, K. B., Denk, D., Ceteci, F., Mohs, K., Engel, E., et al. (2023) · Gut · doi:10.1136/gutjnl-2022-327909 · Cited by 270
Li, L., Wang, L., Li, J., Fan, Z., Li, Y., Zhang, Z., Zhang, C., Yue, D., Qin, G., Zhang, T., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2460 · Cited by 267
“Depletion of MDSCs or inhibiting MDSCs function mitigates cancer progression (52, 53).”
BackgroundLi, S., Yu, W., Xie, F., Luo, H., Liu, Z., Lv, W., Shi, D., Yu, D., Gao, P., Chen, C., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35431-x · Cited by 265
Cancer Stemness Meets Immunity: From Mechanism to Therapy
Chen, P., Hsu, W., Han, J., Xia, Y., & DePinho, R. A. (2021) · Cell Reports · doi:10.1016/j.celrep.2020.108597 · Cited by 255
Theivanthiran, B., Evans, K. S., DeVito, N. C., Plebanek, M. P., Sturdivant, M., Wachsmuth, L. P., Salama, A. K. S., Kang, Y., Hsu, D. S., Balko, J. M., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci133055 · Cited by 255
“Additional work has shown that CXCR2 blockade enhances the efficacy of anti-PD-1 ab immunotherapy in models of both pancreatic cancer and sarcoma (8-10).”
BackgroundClinical cancer immunotherapy: Current progress and prospects
Liu, C., Yang, M., Zhang, D., Chen, M., & Zhu, D. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.961805 · Cited by 261
Chao, T., Furth, E. E., & Vonderheide, R. H. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0188 · Cited by 252
“CXCR2 is also essential for the recruitment of TANs in various cancers (32, 33).”
BackgroundResultStiff, A., Trikha, P., Mundy-Bosse, B., McMichael, E., Mace, T. A., Benner, B., Kendra, K., Campbell, A., Gautam, S., Abood, D., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0691 · Cited by 244
“The presence of immunosuppressive cells like MDSCs in the tumormicroenvironment canbe amajor impediment to immunebased therapies (53).”
BackgroundInhibiting myeloid-derived suppressor cell trafficking enhances T cell immunotherapy
Sun, L., Clavijo, P. E., Robbins, Y. L., Patel, P., Friedman, J., Greene, S., Das, R., Silvin, C., Waes, C. V., Horn, L. A., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.126853 · Cited by 239
“CXCR2 blockade using a commercially available anti–mouse CXCR2 mAb (12).”
MethodThe TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2
Hartwig, T., Montinaro, A., von Karstedt, S., Sevko, A., Šurinová, S., Chakravarthy, A., Taraborrelli, L., Dráber, P., Lafont, É., Vargas, F. A., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.01.021 · Cited by 237
“GR1+ cells (Highfill et al., 2014; Toh et al., 2011), we compared myeloid immune cell infiltration in the microenvironment of FADD-proficient and FADD-deficient tumors.”
BackgroundCXCL5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target
Zhang, W., Wang, H., Sun, M., Deng, X., Wu, X., Ma, Y., Li, M., Shuoa, S. M., You, Q., & Miao, L. (2020) · 癌症：英文版 · doi:10.1002/cac2.12010 · 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
“CCR5 MDSCs have a higher immunosuppressive activity than CCR5 MDSCs (71), and disruption of MDSC trafficking enhances anti-PD1 therapy (72).”
BackgroundThe Programmed Death-1 Immune-Suppressive Pathway: Barrier to Antitumor Immunity
Ostrand‐Rosenberg, S., Horn, L. A., & Haile, S. T. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401572 · Cited by 240
“rhabdomyosarcoma system, monotherapy with anti–PD-1 mAbs had limited therapeutic effect; however, inclusion of mAbs against CXCR2, a receptor expressed by myeloidderived suppressor cells, synergized with Ab therapy (65).”
BackgroundPhenotype, development, and biological function of myeloid-derived suppressor cells
Zhao, Y., Wu, T., Shao, S., Shi, B., & Zhao, Y. X. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1004983 · Cited by 220
“Rhabdomyosarcoma induces robust expansion of CXCR2CCD11bCLy6Ghi MDSCs, and CXCR2 deficiency prevents CD11bCLy6Ghi MDSC tumor trafficking.(18) Thus, CXCR2 is identified as a novel target for modulating tumor immune escape and CXCR2CCD11bCLy6Ghi MDSCs are an important suppressive Table 1.”
BackgroundOrberg, E. T., Fan, H., Tam, A. J., Dejea, C. M., Shields, C. E. D., Wu, S., Chung, L., Finard, B. B., Wu, X., Fathi, P., et al. (2016) · Mucosal Immunology · doi:10.1038/mi.2016.53 · Cited by 230
“BFT-induced production of IL-8 by human CECs, an NF-kB-dependent factor, and its murine homolog, CXCL1, can direct MDSC recruitment.(23,30) Herein, we demonstrated that ETBF has the capacity to shape the inflammatory environment differently in CECApcþ / vs.”
Li, B., Garstka, M. A., & Li, Z. (2019) · Molecular Immunology · doi:10.1016/j.molimm.2019.11.014 · Cited by 223
Stump, C. T., & Dougan, S. K. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.11.011 · Cited by 233
Innate Immunity and Cancer Pathophysiology
Maiorino, L., Daßler‐Plenker, J., Sun, L., & Egeblad, M. (2021) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-032221-115501 · Cited by 233
Targeting CXCR2 inhibits the progression of lung cancer and promotes therapeutic effect of cisplatin
Cheng, Y., Mo, F., Li, Q., Han, X., Shi, H., Chen, S., Wei, Y., & Wei, X. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01355-1 · Cited by 214
“Progression of cancer is usually accompanied with infiltration of MDSCs which makes a delayed treatment of anti-PD1 less benefit [64].”
BackgroundMyeloid-Derived Suppressor Cells in the Tumor Microenvironment
Dysthe, M., & Parihar, R. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-35723-8_8 · Cited by 213
Cancer immunotherapy: it’s time to better predict patients’ response
Pilard, C., Ancion, M., Delvenne, P., Jérusalem, G., Hubert, P., & Herfs, M. F. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01413-x · Cited by 224
Dinh, H. Q., Pan, F., Wang, G., Huang, Q., Olingy, C. E., Wu, Z., Wang, S., Xu, X., Xu, X., He, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27599-5 · Cited by 209
Human Tumor-Infiltrating Myeloid Cells: Phenotypic and Functional Diversity
Elliott, L., Doherty, G. A., Sheahan, K. D., & Ryan, E. J. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00086 · Cited by 219
“In a model of rhabdomyosarcoma, the blocking of CXCR2 prevented the migration of MDSC in to the TME, and interestingly, it also increased the efficacy of PD-1 targeting antibodies (98).”
BackgroundReshaping the Tumor Stroma for Treatment of Pancreatic Cancer
Vennin, C., Murphy, K. J., Morton, J. P., Cox, T. R., Pajic, M., & Timpson, P. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.11.280 · Cited by 207
Opportunities for therapeutic antibodies directed at G-protein-coupled receptors
Hutchings, C. J., Koglin, M., Olson, W. C., & Marshall, F. H. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.91 · Cited by 202
Cancer Vaccines, Adjuvants, and Delivery Systems
Paston, S. J., Brentville, V. A., Symonds, P., & Durrant, L. G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.627932 · Cited by 200
Najjar, Y. G., Rayman, P. A., Jia, X., Pavicic, P. G., Rini, B. I., Tannenbaum, C. S., Ko, J. S., Haywood, S., Cohen, P. A., Hamilton, T. A., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1823 · Cited by 196
“Its ligands, IL8 and CXCL5, have been shown to be chemoattractants for PMN-MDSC (32, 38).”
BackgroundResultInfluentialStudy and analysis of antitumor resistance mechanism of PD1/PD‐L1 immune checkpoint blocker
Wang, Z., & Wu, X. (2020) · Cancer Medicine · doi:10.1002/cam4.3410 · Cited by 205
Argyle, D. J., & Kitamura, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02629 · Cited by 195
Stiff, A., Trikha, P., Wesolowski, R., Kendra, K., Hsu, V., Uppati, S., McMichael, E., Duggan, M., Campbell, A., Keller, K., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-1490 · Cited by 188
“To promote local immune suppression MDSC must migrate into the tumor microenvironment, and disruption of this process may affect anti-tumor immune responses (4,17).”
InfluentialHossain, D. M. S., Pal, S. K., Moreira, D., Duttagupta, P. A., Zhang, Q., Won, H., Jones, J. O., D’Apuzzo, M., Forman, S. J., & Kortylewski, M. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3145 · Cited by 192
“Successful targeting of MDSCs requires identification of functional markers associated with the tumor microenvironment, as shown by promising preclinical results on targeting CXCR2-mediated MDSC tumor trafficking (17).”
Metadata
- Authors
- Highfill, S. L., Cui, Y., Giles, A. J., Smith, J. P., Zhang, H., Morse, E., Kaplan, R. N., & Mackall, C. L.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Mackall, Crystal L.
- Venue
- Science Translational Medicine
- Published
- 2014-05-21
- Volume
- 6
- Issue
- 237
- Pages
- 237ra67-237ra67
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC6980372
- OpenAlex
- W2171524684
- Cited by
- 767
- References
- 50
- Citations by year
- 2026: 55 · 2025: 62 · 2024: 57 · 2023: 83 · 2022: 73 · 2021: 100 · 2020: 91 · 2019: 60 · 2018: 52 · 2017: 52 · 2016: 38 · 2015: 31 · 2014: 12
- FWCI
- 20.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (Z01BC011072, Z01BC010566, Z01SC010289)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- CXCR2, myeloid-derived suppressor cells, tumor immune evasion, anti-PD-1 therapy, rhabdomyosarcoma, pediatric sarcoma, interleukin-8, PD-L1, tumor immunosuppression
- MeSH terms
- Adolescent, Adult, Animals, Antibodies, Monoclonal, Antigens, Ly, Antineoplastic Combined Chemotherapy Protocols, Chemotaxis, Child, Child, Preschool, Female, Humans, Male, Mice, Inbred C57BL, Prognosis, Rhabdomyosarcoma, Time Factors, Neoplastic Stem Cells, Case-Control Studies, Cytokines, Interleukin-8, Mice, Knockout, Tumor Escape, Receptors, Interleukin-8B, CD11b Antigen, Cell Line, Tumor, Tumor Burden, Mice, Chemokine CXCL1, Young Adult, Tumor Microenvironment, B7-H1 Antigen
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
