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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.
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“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]
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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
Items 101–200 of 770
Majzner, R. G., Simon, J. S., Grosso, J. F., Martinez, D., Pawel, B. R., Santi, M., Merchant, M. S., Geoerger, B., Hezam, I., Marty, V., et al. (2017) · Cancer · doi:10.1002/cncr.30724 · Cited by 179
Self-citationCD300ld on neutrophils is required for tumour-driven immune suppression
Wang, C., Zheng, X., Zhang, J., Jiang, X., Wang, J., Li, Y., Li, X., Shen, G., Peng, J., Zheng, P., et al. (2023) · Nature · doi:10.1038/s41586-023-06511-9 · Cited by 182
“CXCR2 inhibitors reduce tumour growth by blocking PMN-MDSC recruitment and show synergistic effects with PD1 antibodies 32,33 .”
BackgroundKabacaoğlu, D., Ciecielski, K. J., Ruess, D. A., & Algül, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01878 · Cited by 181
“In support of this, strategies eliminating immunosuppressive populations in the TME enhanced CTL infiltration in various cancers (152, 153).”
MethodMyeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion
Lu, J., Luo, Y., Rao, D., Wang, T., Lei, Z., Chen, X., Zhang, B., Li, Y., Liu, B., Xia, L., et al. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00505-7 · Cited by 194
“CXCR2 ligands are produced in human pediatric sarcomas and are elevated in the serum when sarcomas metastasize [180].”
BackgroundFusobacterium nucleatum and colorectal cancer: A mechanistic overview
Goradel, N. H., Heidarzadeh, S., Jahangiri, S., Farhood, B., Mortezaee, K., Khanlarkhani, N., & Negahdari, B. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27250 · Cited by 179
“It has been shown that MDSCs reduce infiltration of T cell into tumor (Highfill et al., 2014), increase matrix metalloproteinase 9, which increases angiogenesis (L. Yang et al., 2004), and maintains stemness characteristics (Cui et al., 2013).”
BackgroundMyeloid-Derived Suppressor Cells: A Propitious Road to Clinic
Grover, A., Sanseviero, E., Timosenko, E., & Gabrilovich, D. I. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0764 · Cited by 176
Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy
Jung, K., Heishi, T., Khan, O. F., Kowalski, P. S., Incio, J., Rahbari, N. N., Chung, E., Clark, J. W., Willett, C. G., Luster, A. D., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci93182 · Cited by 164
“Recently, 2 studies revealed that inhibition of granulocyte recruitment into tumors improves the efficacy of the immune checkpoint blockade (35, 41).”
BackgroundOvercoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors
Middelburg, J., Kemper, K., Engelberts, P. J., Labrijn, A. F., Schuurman, J., & van Hall, T. (2021) · Cancers · doi:10.3390/cancers13020287 · Cited by 178
Dominguez, C. L., McCampbell, K. K., David, J. M., & Palena, C. (2017) · JCI Insight · doi:10.1172/jci.insight.94296 · Cited by 169
“Accordingly, disruption of CXCR2 signaling has been shown to prevent PMN-MDSC trafficking to murine rhabdomyosarcoma tumors (16).”
BackgroundRNA Nanotechnology-Mediated Cancer Immunotherapy
Lin, Y., Wang, Y., Blake, S., Yu, M., Mei, L., Wang, H., & Shi, J. (2019) · Theranostics · doi:10.7150/thno.35568 · Cited by 174
“Due to the important role in tumor-associated immune suppression of MDSC, many studies were focused on exploring therapeutic strategies to eliminate these cells or to modulate their functions [132-135].”
BackgroundChoucair, K., Morand, S. M., Stanbery, L., Edelman, G. M., Dworkin, L. D., & Nemunaitis, J. J. (2020) · Cancer Gene Therapy · doi:10.1038/s41417-020-0174-y · Cited by 170
Davis, R. J., Waes, C. V., & Allen, C. T. (2016) · Oral Oncology · doi:10.1016/j.oraloncology.2016.05.002 · Cited by 167
“Indeed, eliminating CXCR2+ MDSCs from the TME enhances responses observed with PD1 targeting immunotherapy in different animal models [38].”
BackgroundInfluentialSharma, R., Kadife, E., Myers, M. A., Kannourakis, G., Prithviraj, P., & Ahmed, N. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01961-3 · Cited by 179
Epithelial-mesenchymal transition and inflammation at the site of the primary tumor
Dominguez, C. L., David, J. M., & Palena, C. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.08.002 · Cited by 163
“Blockade of CXCR2 signaling was also shown to improve the anti-tumor effect of programmed death 1 (PD1) checkpoint blockade, attributed to the alleviation of the immunosuppressive environment originated by the MDSC infiltrate [66].”
BackgroundRegulation of PD-1/PD-L1 pathway and resistance to PD-1/PD-L1 blockade
Bai, J., Gao, Z., Li, X., Dong, L., Han, W., & Nie, J. (2017) · Oncotarget · doi:10.18632/oncotarget.22690 · Cited by 159
“Inhibitors of these chemokine receptors could abrogate immune evasion and improve anti-tumor T cell responses [114].”
BackgroundAntuamwine, B. B., Bosnjakovic, R., Hofmann-Vega, F., Wang, X., Θεοδοσίου, Θ., Iliopoulos, I., & Brandau, S. (2022) · Immunological Reviews · doi:10.1111/imr.13176 · Cited by 160
Giles, A. J., Reid, C. M., Evans, J. D., Murgai, M., Vicioso, Y. M., Highfill, S. L., Kasai, M., Vahdat, L. T., Mackall, C. L., Lyden, D. C., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-0204 · Cited by 161
“MDSCs within a primary tumor possess strong immunosuppressive properties (25-27).”
Self-citationMcDonald, P. C., Chafe, S. C., & Dedhar, S. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2016.00027 · Cited by 154
“MDSC suppress the anti-tumor immune response (Gabrilovich et al., 2012), therapeutic efforts to restore this response (Highfill et al., 2014; Kim et al., 2014), as well as limit the efficacy of anti-angiogenic (Shojaei et al., 2007, 2009) and chemotherapies (Acharyya et al., 2012).”
BackgroundInfluentialTurn Back the TIMe: Targeting Tumor Infiltrating Myeloid Cells to Revert Cancer Progression
Awad, R. M., Vlaeminck, Y. D., Maebe, J., Goyvaerts, C., & Breckpot, K. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01977 · Cited by 154
“A line of thought that is reinforced by the observation that MDSC depletion in experimental models was shown to enhance antitumor immune responses and overcome resistance (133).”
BackgroundMi, Y., Guo, N., Luan, J., Cheng, J., Hu, Z., Jiang, P., Jin, W., & Gao, X. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00737 · Cited by 155
“The chemokine receptor CXCR2 is a receptor of CXCL2 which was highly expressed in PMN-MDSC, andplay an important role in MDSCs recruitment (122).”
BackgroundHeim, C. E., Vidlak, D., Scherr, T. D., Hartman, C. W., Garvin, K. L., & Kielian, T. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1402689 · Cited by 148
Sasso, M. S., Lollo, G., Pitorre, M., Solito, S., Pinton, L., Valpione, S., Bastiat, G., Mandruzzato, S., Bronte, V., Marigo, I., et al. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.04.010 · Cited by 150
Hou, A., Hou, K., Huang, Q., Lei, Y., & Chen, W.-L. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00783 · Cited by 148
“It seems that the functional, biochemical and genomic characterization of PMN-MDSCs described in many studies is conducted for the entire population of cells, not for PMN-MDSCs only.”
BackgroundInfluentialMorisada, M. V., Clavijo, P. E., Moore, E. C., Sun, L., Chamberlin, M. M., Waes, C. V., Hodge, J. W., Mitchell, J. B., Friedman, J., & Allen, C. T. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1395996 · Cited by 150
Therapeutic Immune Modulation against Solid Cancers with Intratumoral Poly-ICLC: A Pilot Trial
Kyi, C., Roudko, V., Sabado, R. L., Saenger, Y. M., Loging, W., Mandeli, J., Thin, T. H., Lehrer, D., Donovan, M. J., Posner, M. R., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1866 · Cited by 148
“Both cytokines are ligands of the CXCR2 receptor, activation of which in tumors has been shown to interfere with PD-1/PD-L1 immunotherapies in preclinical studies (28, 29).”
BackgroundImmune regulation of metastasis: mechanistic insights and therapeutic opportunities
Blomberg, O. S., Spagnuolo, L., & de Visser, K. E. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.036236 · Cited by 145
“…recruitment through CXCR2 blockade prevented metastasis formation in cell line, xenograft and spontaneous models of rhabdomyosarcoma, colon and pancreatic cancer (Highfill et al., 2014; Steele et al., 2016; Wang et al., 2017), and several CXCR2 inhibitors are currently under clinical investigation.”
Ogawa, R., Yamamoto, T. S., Hirai, H., Hanada, K., Kiyasu, Y., Nishikawa, G., Mizuno, R., Inamoto, S., Itatani, Y., Sakai, Y., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3684 · Cited by 144
Targeting myeloid chemotaxis to reverse prostate cancer therapy resistance
Guo, C. W., Sharp, A., Gürel, B., Crespo, M., Figueiredo, I., Jain, S., Vogl, U. M., Rekowski, J., Rouhifard, M., Gallagher, L., et al. (2023) · Nature · doi:10.1038/s41586-023-06696-z · Cited by 149
“In models of different tumours, including prostate cancer, CXCR2 inhibition blocks the recruitment of tumour-infiltrating PMN-MDSCs leading to tumour suppression 10,12,14,24,25 .”
BackgroundApoptosis-induced CXCL5 accelerates inflammation and growth of prostate tumor metastases in bone
Roca, H., Jones, J., Purica, M. C., Weidner, S., Koh, A. J., Kuo, R., Wilkinson, J. E., Wang, Y., Daignault‐Newton, S., Pienta, K. J., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92466 · Cited by 140
“Furthermore, in a model of rhabdomyosarcoma, it was demonstrated that antibody-mediated neutralization of CXCR2 (a receptor for CXCL5) enhanced anti-PD1 effectiveness by preventing the tumor infiltration of the CD11b+Ly6Ghi suppressor cells (54).”
BackgroundKim, W., Chu, T. H., Nienhüser, H., Jiang, Z., Portillo, A. D., Remotti, H. E., White, R. A., Hayakawa, Y., Tomita, H., Fox, J. G., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.10.036 · Cited by 141
Immune-mediated mechanisms influencing the efficacy of anticancer therapies
Coffelt, S. B., & de Visser, K. E. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.02.006 · Cited by 147
“For instance, blockade of CXCR2-mediated MDSC trafficking into transplanted rhabdomyosarcomas increases the efficacy of anti-PD1 therapy [186].”
BackgroundCombination Approaches with Immune-Checkpoint Blockade in Cancer Therapy
Swart, M., Verbrugge, I., & Beltman, J. B. (2016) · Frontiers in Oncology · doi:10.3389/fonc.2016.00233 · Cited by 141
“C chemokine receptor 1 (CCR1) or CXC chemokine receptor 2 (CXCR2) (126, 127).”
BackgroundInfluentialHow to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions
Bruger, A. M., Dorhoi, A., Esendağlı, G., Barczyk‐Kahlert, K., van der Bruggen, P., Lipoldová, M., Perečko, T., Santibanez, J. F., Saraiva, M., Ginderachter, J. A. V., et al. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2170-8 · Cited by 137
Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy
Han, Z., Li, Y.-B., Yang, L., Cheng, H., Liu, X., & Chen, H. (2021) · Molecules · doi:10.3390/molecules27010137 · Cited by 145
“CXCR2 inhibition prevented MDSC trafficking to the TME and improved the efficacy of anti-PD-1 therapy [90].”
BackgroundBeyond Cell Motility: The Expanding Roles of Chemokines and Their Receptors in Malignancy
Morein, D., Erlichman, N., & Ben‐Baruch, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00952 · Cited by 138
“This study has revealed a regulatory loop in which genotoxic stress created by chemotherapeutic drugs limited the survival of breast tumor cells, but the expression of tumor necrosis factor α (TNFα) was also increased and has led to elevated production of CXCL1/2 by the tumor cells; these chemokines recruited CXCR2-ex…”
BackgroundInfluentialYaseen, M. M., Abuharfeil, N. M., Darmani, H., & Daoud, A. K. (2020) · Open Biology · doi:10.1098/rsob.200111 · Cited by 138
Liu, Y., Wong, C. C., Ding, Y., Gao, M., Wen, J., Lau, H. C.-H., Cheung, A. H. K., Huang, D., Huang, H., & Yu, J. Q. (2024) · Nature Microbiology · doi:10.1038/s41564-024-01695-w · Cited by 143
“Chemotaxis of MDSCs is primarily driven by tumour cell-derived chemokines 18 .”
The Role of Chemokines in Promoting Colorectal Cancer Invasion/Metastasis
Itatani, Y., Kawada, K., Inamoto, S., Yamamoto, T. S., Ogawa, R., Taketo, M. M., & Sakai, Y. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17050643 · Cited by 140
Baci, D., Bosi, A., Gallazzi, M., Rizzi, M., Noonan, D. M., Poggi, A. D., Bruno, A., & Mortara, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093125 · Cited by 133
“Some studies have reported an increased effect of combining CXCR2 inhibitors or anti-Ly6G and checkpoint inhibitors that boost the immune system against tumor growth and dissemination [91] (Figure 2B).”
BackgroundYang, R., Li, Y., Wang, H., Qin, T., Yin, X., & Ma, X. (2022) · Molecular Biomedicine · doi:10.1186/s43556-022-00071-6 · Cited by 141
Kumar, S., Chatterjee, M., Ghosh, P., Ganguly, K. K., Basu, M., & Ghosh, M. K. (2022) · Genes & Diseases · doi:10.1016/j.gendis.2022.07.024 · Cited by 135
“Furthermore, the inhibition of chemokine receptors also help to strengthen the efficacy of PD-1/PD-L1 blockade.(121,122) Various other combinatorial strategies (viz.”
BackgroundYofe, I., Shami, T., Cohen, N., Landsberger, T., Sheban, F., Stoler-Barak, L., Yalin, A., Phan, T. S., Li, B., Monteran, L., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0299 · Cited by 130
“Interestingly, the Cxcl2–Cxcr2 signaling axis (41) was upregulated in distal normal tissues, suggesting that this pathway contributes to immune suppression in distal areas of metastases-bearing lungs that do not contain metastatic lesions.”
Chemotherapy and immunotherapy: mapping the road ahead
Cook, A., Lesterhuis, W. J., Nowak, A. K., & Lake, R. (2015) · Current Opinion in Immunology · doi:10.1016/j.coi.2015.12.003 · Cited by 134
Lesina, M., Wörmann, S. M., Morton, J. P., Diakopoulos, K. N., Korneeva, O., Wimmer, M., Einwächter, H., Sperveslage, J., Demir, İ. E., Kehl, T., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86477 · Cited by 134
Beyond the Barrier: Unraveling the Mechanisms of Immunotherapy Resistance
Bell, H. N., & Zou, W. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-101819-024752 · Cited by 143
Mechanisms of resistance to immune checkpoint inhibitors
Nagasaki, J., Ishino, T., & Togashi, Y. (2022) · Cancer Science · doi:10.1111/cas.15497 · Cited by 130
Immunobiology of cholangiocarcinoma
Loeuillard, E. J., Conboy, C. B., Gores, G. J., & Ilyas, S. I. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.06.003 · Cited by 123
Zhou, Z., Xia, G., Xiang, Z., Liu, M., Wei, Z., Yan, J., Chen, W., Zhu, J., Awasthi, N., Sun, X., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3567 · Cited by 125
“CXCR2-targeted therapies can enhance the efficacy of immunotherapy in several solid tumors (4, 5) and increase the sensitivity of chemotherapy (6).”
BackgroundInfluentialAlicea-Torres, K. M., Sanseviero, E., Gui, J., Chen, J., Veglia, F., Yu, Q., Donthireddy, L., Kossenkov, A. V., Lin, C., Fu, S., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22033-2 · Cited by 123
Recent advances in the clinical development of immune checkpoint blockade therapy
Ghahremanloo, A., Soltani, A., Modaresi, S. M. S., & Hashemy, S. I. (2019) · Cellular Oncology · doi:10.1007/s13402-019-00456-w · Cited by 119
“Similarly, other studies have indicated that MDSC blockade can induce the effectiveness of PD-1 blockade [93, 94].”
ResultImmune checkpoint blockade opens a new way to cancer immunotherapy
Sadreddini, S., Baradaran, B., Aghebati‐Maleki, A., Sadreddini, S., Shanehbandi, D., Fotouhi, A., & Maleki, L. A. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27816 · Cited by 119
“have inhibitory roles against the antitumor defense (Highfill et al., 2014).”
BackgroundThe Role of Selected Chemokines and Their Receptors in the Development of Gliomas
Groblewska, M., Litman‐Zawadzka, A., & Mroczko, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103704 · Cited by 121
Reprogramming immunosuppressive myeloid cells facilitates immunotherapy for colorectal cancer
Lu, W., Yu, W., He, J., Liu, W., Yang, J., Lin, X., Zhang, Y., Wang, X., Jiang, W., Luo, J., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202012798 · Cited by 112
“IMCs, including TAMs and MDSCs, are the major drivers of an immunosuppressive tumor microenvironment and can contribute to resistance to ICB therapy (Highfill et al, 2014; De Henau et al, 2016), highlighting the potential for further improvements by combining specific IMC-targeted therapeutics.”
BackgroundSelf-citationJoshi, S., & Durden, D. L. (2019) · Journal of Oncology · doi:10.1155/2019/5245034 · Cited by 120
“The roles of CCL2, CCL5, CCL7, and CXCL8 and their receptors, CCR2 and CCR4, in the recruitment of MDSCs are well described [124].”
BackgroundZhao, D., Cai, L., Lü, X., Liang, X., Li, J., Chen, P., Ittmann, M., Shang, X., Jiang, S., Li, H., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1352 · Cited by 116
“The poor response of prostate cancer to ICI in the clinic (23) and the key role of MDSCs in suppressing ICI responsiveness in mouse models (28,35,46,47), prompted us to test whether inhibition of the CHD1/IL-6 pathway would improve ICI responsiveness in various mouse models of prostate cancer.”
BackgroundThe Role of Prostaglandin E 2 in Tumor-Associated Immunosuppression
Wang, D., & DuBois, R. N. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.11.003 · Cited by 114
“The observation that inhibition of tumor-infiltrating MDSCs enhanced anti-PD1 efficacy in rhabdomyosarcoma in vivo (10) supports this notion.”
BackgroundZhang, Y., Liu, G., Sun, M., & Lü, X. (2020) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2019.0372 · Cited by 113
Liu, C., Chen, Z., Chen, K., Liao, F.-T., Chung, C.-E., Liu, X., Lin, Y., Keohavong, P., Leikauf, G. D., & Di, Y. P. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-1994 · Cited by 114
Bozkus, C. C., Elzey, B. D., Crist, S. A., Ellies, L. G., & Ratliff, T. L. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500959 · Cited by 112
“Indeed, several studies demonstrated that depletion of MDSCs or inhibiting MDSC function impaired cancer progression (31, 32).”
BackgroundCircadian regulation of cancer cell and tumor microenvironment crosstalk
Xuan, W., Khan, F., James, C. D., Heimberger, A. B., Lesniak, M. S., & Chen, P. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.06.008 · Cited by 113
Targeting myeloid-derived suppressor cells for cancer immunotherapy
Liu, Y., Wei, G., Cheng, W. A., Dong, Z., Sun, H., Lee, V. Y., Cha, S.-C., Smith, D. L., Kwak, L. W., & Qin, H. (2018) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-018-2175-3 · Cited by 110
“Finally, blocking chemokine CXCR2 signaling via antiCXCR2 mAb treatment disrupts CXCR2-mediated MDSC tumor infiltration, and improves the efficacy of checkpoint blockade by anti-PD1 therapy [120].”
BackgroundNeutrophil: A New Player in Metastatic Cancers
Wu, M., Ma, M., Tan, Z., Zheng, H., & Liu, X. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.565165 · Cited by 105
“Indeed, preclinical studies have shown that combination of anti-PD-1 inhibitor with anti-CXCR2 treatment has synergistic effect to delay tumor growth (145).”
BackgroundCXCR2+ MDSCs promote breast cancer progression by inducing EMT and activated T cell exhaustion
Zhu, H., Gu, Y., Xue, Y., Yuan, M., Cao, X., & Liu, Q. (2017) · Oncotarget · doi:10.18632/oncotarget.23020 · Cited by 102
“The phenotype of M-MDSCs is CD11b+Ly6G-Ly6Chi and G-MDSCs is CD11b+Ly6G+Ly6Clo/−.”
BackgroundInfluentialCurrent Progresses and Challenges of Immunotherapy in Triple-Negative Breast Cancer
Mediratta, K., El‐Sahli, S., D’Costa, V. M., & Wang, L. (2020) · Cancers · doi:10.3390/cancers12123529 · Cited by 102
“showed that early treatments with anti-PD-1 agents prevented tumor growth, but late treatments showed less benefit due to the presence of MDSCs in the TME [102].”
BackgroundYu, G., Bu, L., Huang, C., Zhang, W., Chen, W.-J., Gutkind, J. S., Kulkarni, A. B., & Sun, Z. (2015) · Oncotarget · doi:10.18632/oncotarget.5955 · Cited by 101
“Oncotarget42075www.impactjournals.com/oncotarget Oncotarget42076www.impactjournals.com/oncotarget More recent reports have suggested the close relationship of PD-1/PD-L1 with MDSCs and TAMs [32].”
InfluentialSteinberg, S. M., Shabaneh, T. B., Zhang, P., Martyanov, V., Li, Z., Malik, B. T., Wood, T. A., Boni, A., Molodtsov, A. K., Angeles, C. V., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-1755 · Cited by 102
“However, there is precedence for CXCR2 (the cognate receptor for CXCL3) mediating granulocytic MDSC trafficking into tumors (32), and for CX3CR1 (the cognate receptor for CX3CL1) as a marker of some tumor-infiltrating MDSCs (33).”
Sinitski, D., Kontos, C., Krammer, C., Asare, Y., Kapurniotu, A., & Bernhagen, J. (2019) · Thrombosis and Haemostasis · doi:10.1055/s-0039-1677803 · Cited by 97
CD200 promotes immunosuppression in the pancreatic tumor microenvironment
Choueiry, F., Torok, M. A., Shakya, R., Agrawal, K., Deems, A., Benner, B. N., Hinton, A. M., Shaffer, J. L., Blaser, B. W., Noonan, A. M., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000189 · Cited by 100
Immune cells as tumor drug delivery vehicles
Combes, F., Meyer, E., & Sanders, N. N. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.07.043 · Cited by 99
“Conversely, the highly CXCR2-dependent recruitment of PMN-MDSCs into the TME can be blocked either by monoclonal antibodies [245] or by small molecule inhibitors [246].”
BackgroundPatel, R. R., He, K., Barsoumian, H. B., Chang, J. Y., Tang, C. Z., Verma, V., Comeaux, N. I., Chun, S. G., Gandhi, S. J., Truong, M. T., et al. (2021) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2021.06.037 · Cited by 105
A positive crosstalk between CXCR4 and CXCR2 promotes gastric cancer metastasis
Xiang, Z., Zhou, Z.-J., Xia, G.-K., Zhang, X.-H., Wei, Z.-W., Zhu, J.-T., Yu, J., WenYing, C. H. E. N., He, Y., Schwarz, R. E., et al. (2017) · Oncogene · doi:10.1038/onc.2017.108 · Cited by 97
Zhang, C., Xia, D., Liu, J., Huo, D., Jiang, X., & Hu, Y. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202000189 · Cited by 96
Li, T., Liu, T., Zhu, W., Xie, S., Zhao, Z., Feng, B., Guo, H., & Yang, R. (2021) · Clinical Medicine Insights Oncology · doi:10.1177/11795549211035540 · Cited by 98
Zalfa, C., & Paust, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.633205 · Cited by 100
“CXCR1/2 inhibitors (SX-682) significantly abrogated MDSCs trafficking within a tumor and improved tumor infiltration, activation, and therapeutic efficacy of adoptively transferred murine NK cells in the HNSCC preclinical model (394), and in combination with anti-PD-1, they improved ICI therapy (395).”
BackgroundCooperation of Oncolytic Herpes Virotherapy and PD-1 Blockade in Murine Rhabdomyosarcoma Models
Chen, C., Wang, P.-Y., Hutzen, B. J., Sprague, L., Swain, H. M., Love, J., Stanek, J. R., Boon, L., Conner, J., & Cripe, T. P. (2017) · Scientific Reports · doi:10.1038/s41598-017-02503-8 · Cited by 92
Pharmacological Characterization of AZD5069, a Slowly Reversible CXC Chemokine Receptor 2 Antagonist
Nicholls, D., Wiley, K. E., Dainty, I. A., MacIntosh, F., Phillips, C., Gaw, A. J., & Mårdh, C. K. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.221358 · Cited by 93
“Recent advances indicate that chronic inflammation is a key risk factor for cancer, and there are several associations between CXCR2 and cancer (Jamieson et al., 2012; Katoh et al., 2013; Highfill et al., 2014).”
BackgroundClavijo, P. E., Moore, E., Chen, J.-H., Davis, R. J., Friedman, J., Kim, Y., Waes, C. V., Chen, Z., & Allen, C. (2017) · OncoTarget · doi:10.18632/oncotarget.18437 · Cited by 87
“Our data and the work of others [11, 12, 22] demonstrating that the CXCR2 signaling axis appears to play a significant role in the recruitment of gMDSCs in the TME suggests that disruption of this pathway has therapeutic potential.”
Hajizadeh, F., Maleki, L. A., Alexander, M., Mikhailova, M. V., Masjedi, A., Ahmadpour, M., Hashemi, V., & Jadidi‐Niaragh, F. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118699 · Cited by 91
Varayathu, H., Sarathy, V., Thomas, B. E., Mufti, S. S., & Naik, R. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.559161 · Cited by 96
Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches
Thyagarajan‐Sahu, A., Alshehri, M. S. A., Miller, K. L., Sherwin, C. M. T., Travers, J. B., & Sahu, R. P. (2019) · Cancers · doi:10.3390/cancers11111627 · Cited by 95
Roles of STAT3 in the pathogenesis and treatment of glioblastoma
Fu, W., Hou, X., Dong, L., & Hou, W. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1098482 · Cited by 94
“Currently, blocking the MDSC recruitment to the tumor microenvironment could increase the susceptibility of cancer cells to anti-PD-L1 therapy (Highfill et al., 2014).”
BackgroundMyeloid‐Derived Suppressor Cells and Therapeutic Strategies in Cancer
Katoh, H., & Watanabe, M. (2015) · Mediators of Inflammation · doi:10.1155/2015/159269 · Cited by 91
Chang, R. B., & Beatty, G. L. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mir0320-475r · Cited by 99
Kersten, K., Salvagno, C., & de Visser, K. E. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00516 · Cited by 92
“Blockade of CXCR2 improves the therapeutic efficacy of anti-PD-1 treatment resulting in a significant survival benefit (139).”
BackgroundHorn, L. A., Riskin, J., Hempel, H., Fousek, K., Lind, H., Hamilton, D. H., McCampbell, K. K., Maeda, D. Y., Zebala, J. A., Su, Z., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000326 · Cited by 90
The Resistance Mechanisms of Lung Cancer Immunotherapy
Wang, F., Wang, S., & Zhou, Q. H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.568059 · Cited by 90
“Specific chemokines, such as CCL5, CCL7, and CXCL8, play an important role in the recruitment of Tregs and MDSCs to the TME, consequently boosting an immunosuppressive climate (204).”
BackgroundDeVito, N. C., Sturdivant, M. S., Thievanthiran, B., Xiao, C., Plebanek, M. P., Salama, A. K. S., Beasley, G. M., Holtzhausen, A., Novotny‐Diermayr, V., Strickler, J. H., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2021.109071 · Cited by 91
“Indeed, we found OMP-18R5 to inhibit Wnt5a-dependent CXCL5 expression and YAP1 stabilization by BP melanoma cells in vitro, as well as CXCL5 expression by BP melanomas in vivo (Figures 6A–6C).”
InfluentialPore, N., Wu, S., Standifer, N., Jure-Kunkel, M., de los Reyes, M., Shrestha, Y., Halpin, R., Rothstein, R., Mulgrew, K., Blackmore, S., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1543 · Cited by 88
“CT26 STK11 KO clone 26C16 tumors were resistant to anti-OX40, anti-CD137 and anti-ICOS agonist antibodies, whereas CT26 STK11wt tumors were highly sensitive (Supplementary Figure S8A-B), indicating that the resistance phenotype extended beyond CPIs.”
BackgroundInfluentialPandey, P. R., Young, K. H., Kumar, D., & Jain, N. K. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01528-6 · Cited by 89
Immune Evasion by Head and Neck Cancer: Foundations for Combination Therapy
Horton, J. D., Knochelmann, H. M., Day, T. A., Paulos, C. M., & Neskey, D. M. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.02.007 · Cited by 93
How neutrophils promote metastasis
Tüting, T., & de Visser, K. E. (2016) · Science · doi:10.1126/science.aaf7300 · Cited by 87
Li, S., Wang, Q., Shen, Y., Hassan, M., Shen, J., Jiang, W., Su, Y., Chen, J., Bai, L., Zhou, W., et al. (2019) · Nano Letters · doi:10.1021/acs.nanolett.9b03753 · Cited by 86
Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy
Yuan, Y. J., Adam, A., Zhao, C., & Chen, H. (2021) · Cancers · doi:10.3390/cancers13040663 · Cited by 87
“CXCR2relied migration and recruitment of a granulocytic subset of MDSCs (PMN-MDSCs) play a role in suppressing CD8+ T-cell infiltration and function, therefore leading to adaptive resistance [61,62].”
BackgroundRoles of Neutrophils in Glioma and Brain Metastases
Lin, Y.-J., Wei, K., Chen, P., Lim, M. K., & Hwang, T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.701383 · Cited by 88
Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis
Neo, S., Tong, L., Chong, J., Liu, Y., Xu, J., Oliveira, M. M. S., Chen, Y., Chen, Z., Lee, K., Burduli, N., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adi2952 · Cited by 91
Keeley, T. S., Costanzo-Garvey, D. L., & Cook, L. M. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.10.013 · Cited by 84
Chamseddine, A. N., Assi, T., Mir, O., & Chouaïb, S. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107986 · Cited by 89
Tumor regulation of the tissue environment in the liver
Eggert, T., & Greten, T. F. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.005 · Cited by 86
“receptor by anti-CXCR2-monoclonal antibody therapy enhanced antiPD-1 antibody treatment success (Highfill et al., 2014).”
BackgroundInfluentialCXCL5: A coachman to drive cancer progression
Deng, J., Jiang, R., Meng, E., & Wu, H. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.944494 · Cited by 83
Gauttier, V., Pengam, S., Durand, J., Biteau, K., Mary, C., Morello, A., Néel, M., Porto, G., Teppaz, G., Thépenier, V., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci135528 · Cited by 84
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
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