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An Oncogenic Alteration Creates a Microenvironment that Promotes Tumor Progression by Conferring a Metabolic Advantage to Regulatory T Cells

熊谷, 尚悟 名古屋大学

2021.06.29

概要

Only a small percentage of patients afflicted with gastric cancer (GC) respond to immune checkpoint blockade (ICB). To study the mechanisms underlying this resistance, we examined the immune landscape of GC. A subset of these tumors was characterized by high frequencies of regulatory T (Treg) cells and low numbers of effector T cells. Genomic analyses revealed that these tumors bore mutations in RHOA that are known to drive tumor progression. RHOA mutations in cancer cells activated the PI3K-AKT-mTOR signaling pathway, increasing production of free fatty acids that are more effectively consumed by Treg cells than effector T cells. RHOA mutant tumors were resistant to PD-1 blockade but responded to combination of PD-1 blockade with inhibitors of the PI3K pathway or therapies targeting Treg cells. We propose that the metabolic advantage conferred by RHOA mutations enables Treg cell accumulation within GC tumors, generating an immunosuppressive TME that underlies resistance to ICB.

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参考文献

Ali, K., Soond, D.R., Pineiro, R., Hagemann, T., Pearce, W., Lim, E.L., Bouabe, H., Scudamore, C.L., Hancox, T., Maecker, H., et al. (2014). Inactivation of PI(3) K p110d breaks regulatory T-cell-mediated immune tolerance to cancer. Nature 510, 407–411.

Angelin, A., Gil-de-Go´ mez, L., Dahiya, S., Jiao, J., Guo, L., Levine, M.H., Wang, Z., Quinn, W.J., 3rd, Kopinski, P.K., Wang, L., et al. (2017). Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments. Cell Metab. 25, 1282–1293.

Ayers, M., Lunceford, J., Nebozhyn, M., Murphy, E., Loboda, A., Kaufman, D.R., Albright, A., Cheng, J.D., Kang, S.P., Shankaran, V., et al. (2017). IFNg-related mRNA profile predicts clinical response to PD-1 blockade. J. Clin. Invest. 127, 2930–2940.

Bae, C.D., Min, D.S., Fleming, I.N., and Exton, J.H. (1998). Determination of interaction sites on the small G protein RhoA for phospholipase D. J. Biol. Chem. 273, 11596–11604.

Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D.R., Steins, M., Ready, N.E., Chow, L.Q., Vokes, E.E., Felip, E., Holgado, E., et al. (2015). Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N. Engl. J. Med. 373, 1627–1639.

Cancer Genome Atlas Research Network (2014). Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513, 202–209.

Chang, C.H., Qiu, J., O’Sullivan, D., Buck, M.D., Noguchi, T., Curtis, J.D., Chen, Q., Gindin, M., Gubin, M.M., van der Windt, G.J., et al. (2015). Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression. Cell 162, 1229–1241.

Cipolletta, D., Feuerer, M., Li, A., Kamei, N., Lee, J., Shoelson, S.E., Benoist, C., and Mathis, D. (2012). PPAR-g is a major driver of the accumulation and phenotype of adipose tissue Treg cells. Nature 486, 549–553.

Curiel, T.J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., EvdemonHogan, M., Conejo-Garcia, J.R., Zhang, L., Burow, M., et al. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med. 10, 942–949.

Currie, E., Schulze, A., Zechner, R., Walther, T.C., and Farese, R.V., Jr. (2013). Cellular fatty acid metabolism and cancer. Cell Metab. 18, 153–161.

Duvel, K., Yecies, J.L., Menon, S., Raman, P., Lipovsky, A.I., Souza, A.L., € Triantafellow, E., Ma, Q., Gorski, R., Cleaver, S., et al. (2010). Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol. Cell 39, 171–183.

Fan, M.Y., and Turka, L.A. (2018). Immunometabolism and PI(3)K Signaling As a Link between IL-2, Foxp3 Expression, and Suppressor Function in Regulatory T Cells. Front. Immunol. 9, 69.

Fridman, W.H., Page` s, F., Saute` s-Fridman, C., and Galon, J. (2012). The immune contexture in human tumours: impact on clinical outcome. Nat. Rev. Cancer 12, 298–306.

Fruman, D.A., Chiu, H., Hopkins, B.D., Bagrodia, S., Cantley, L.C., and Abraham, R.T. (2017). The PI3K Pathway in Human Disease. Cell 170, 605–635.

Gatenby, R.A., and Gillies, R.J. (2004). Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer 4, 891–899.

Gerriets, V.A., Kishton, R.J., Johnson, M.O., Cohen, S., Siska, P.J., Nichols, A.G., Warmoes, M.O., de Cubas, A.A., MacIver, N.J., Locasale, J.W., et al. (2016). Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression. Nat. Immunol. 17, 1459–1466.

Gorbachev, A.V., Kobayashi, H., Kudo, D., Tannenbaum, C.S., Finke, J.H., Shu, S., Farber, J.M., and Fairchild, R.L. (2007). CXC chemokine ligand 9/ monokine induced by IFN-gamma production by tumor cells is critical for T cell-mediated suppression of cutaneous tumors. J Immunol. 178, 2278–2286.

Gouw, A.M., Eberlin, L.S., Margulis, K., Sullivan, D.K., Toal, G.G., Tong, L., Zare, R.N., and Felsher, D.W. (2017). Oncogene KRAS activates fatty acid synthase, resulting in specific ERK and lipid signatures associated with lung adenocarcinoma. Proc. Natl. Acad. Sci. USA 114, 4300–4305.

Griffith, J.W., Sokol, C.L., and Luster, A.D. (2014). Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu. Rev. Immunol. 32, 659–702

Harikumar, K.B., Yester, J.W., Surace, M.J., Oyeniran, C., Price, M.M., Huang, W.C., Hait, N.C., Allegood, J.C., Yamada, A., Kong, X., et al. (2014). K63-linked polyubiquitination of transcription factor IRF1 is essential for IL-1-induced production of chemokines CXCL10 and CCL5. Nat. Immunol. 15, 231–238.

Hensbergen, P.J., Wijnands, P.G., Schreurs, M.W., Scheper, R.J., Willemze, R., and Tensen, C.P. (2005). The CXCR3 targeting chemokine CXCL11 has potent antitumor activity in vivo involving attraction of CD8+ T lymphocytes but not inhibition of angiogenesis. J Immunother. 28, 343–351.

Ho, P.C., and Kaech, S.M. (2017). Reenergizing T cell anti-tumor immunity by harnessing immunometabolic checkpoints and machineries. Curr. Opin. Immunol. 46, 38–44.

Hoelzinger, D.B., Smith, S.E., Mirza, N., Dominguez, A.L., Manrique, S.Z., and Lustgarten, J. (2010). Blockade of CCL1 inhibits T regulatory cell suppressive function enhancing tumor immunity without affecting T effector responses. J Immunol. 184, 6833–6842.

Janku, F., Yap, T.A., and Meric-Bernstam, F. (2018). Targeting the PI3K pathway in cancer: are we making headway? Nat. Rev. Clin. Oncol. 15, 273–291.

Jia, S., Liu, Z., Zhang, S., Liu, P., Zhang, L., Lee, S.H., Zhang, J., Signoretti, S., Loda, M., Roberts, T.M., and Zhao, J.J. (2008). Essential roles of PI(3)Kp110beta in cell growth, metabolism and tumorigenesis. Nature 454, 776–779. 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). Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nat. Med. 22, 851–860.

Kakiuchi, M., Nishizawa, T., Ueda, H., Gotoh, K., Tanaka, A., Hayashi, A., Yamamoto, S., Tatsuno, K., Katoh, H., Watanabe, Y., et al. (2014). Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma. Nat. Genet. 46, 583–587.

Kamada, T., Togashi, Y., Tay, C., Ha, D., Sasaki, A., Nakamura, Y., Sato, E., Fukuoka, S., Tada, Y., Tanaka, A., et al. (2019). PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proc Natl Acad Sci USA. 116, 9999–10008.

Kang, Y.K., Boku, N., Satoh, T., Ryu, M.H., Chao, Y., Kato, K., Chung, H.C., Chen, J.S., Muro, K., Kang, W.K., et al. (2017). Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390, 2461–2471.

Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., and Salzberg, S.L. (2013). TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36.

Kishore, M., Cheung, K.C.P., Fu, H., Bonacina, F., Wang, G., Coe, D., Ward, E.J., Colamatteo, A., Jangani, M., Baragetti, A., et al. (2017). Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis. Immunity 47, 875–889.

Li, H., and Durbin, R. (2009). Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754–1760.

Li, L., Liu, X., Sanders, K.L., Edwards, J.L., Ye, J., Si, F., Gao, A., Huang, L., Hsueh, E.C., Ford, D.A., et al. (2019). TLR8-Mediated Metabolic Control of Human Treg Function: A Mechanistic Target for Cancer Immunotherapy. Cell Metab. 29, 103–123.

Macintyre, A.N., Finlay, D., Preston, G., Sinclair, L.V., Waugh, C.M., Tamas, P., Feijoo, C., Okkenhaug, K., and Cantrell, D.A. (2011). Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism. Immunity 34, 224–236.

Maeda, Y., Nishikawa, H., Sugiyama, D., Ha, D., Hamaguchi, M., Saito, T., Nishioka, M., Wing, J.B., Adeegbe, D., Katayama, I., and Sakaguchi, S. (2014). Detection of self-reactive CD8+ T cells with an anergic phenotype in healthy individuals. Science 346, 1536–1540.

Mantovani, A., Marchesi, F., Malesci, A., Laghi, L., and Allavena, P. (2017). Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol. 14, 399–416.

Michalek, R.D., Gerriets, V.A., Jacobs, S.R., Macintyre, A.N., MacIver, N.J., Mason, E.F., Sullivan, S.A., Nichols, A.G., and Rathmell, J.C. (2011). Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 186, 3299–3303.

Miyara, M., Yoshioka, Y., Kitoh, A., Shima, T., Wing, K., Niwa, A., Parizot, C., Taflin, C., Heike, T., Valeyre, D., et al. (2009). Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30, 899–911.

Muraoka, D., Kato, T., Wang, L., Maeda, Y., Noguchi, T., Harada, N., Takeda, K., Yagita, H., Guillaume, P., Luescher, I., et al. (2010). Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8+ T cells. J Immunol. 185, 3768–3776.

Muroski, M.E., Miska, J., Chang, A.L., Zhang, P., Rashidi, A., Moore, H., Lopez-Rosas, A., Han, Y., and Lesniak, M.S. (2017). Fatty Acid Uptake in T Cell Subsets Using a Quantum Dot Fatty Acid Conjugate. Sci. Rep. 7, 5790.

Nagarsheth, N., Wicha, M.S., and Zou, W. (2017). Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat. Rev. Immunol. 17, 559–572.

Okkenhaug, K., Patton, D.T., Bilancio, A., Garcon, F., Rowan, W.C., and Vanhaesebroeck, B. (2006). The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells. J Immunol. 177, 5122–5128.

Patton, D.T., Garden, O.A., Pearce, W.P., Clough, L.E., Monk, C.R., Leung, E., Rowan, W.C., Sancho, S., Walker, L.S., Vanhaesebroeck, B., and Okkenhaug, K. (2006). Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+ CD25+ Foxp3+ regulatory T cells. J Immunol. 177, 6598–6602.

Peng, W., Chen, J.Q., Liu, C., Malu, S., Creasy, C., Tetzlaff, M.T., Xu, C., McKenzie, J.A., Zhang, C., Liang, X., et al. (2016). Loss of PTEN Promotes Resistance to T Cell-Mediated Immunotherapy. Cancer Discov. 6, 202–216.

Peterson, T.R., Sengupta, S.S., Harris, T.E., Carmack, A.E., Kang, S.A., Balderas, E., Guertin, D.A., Madden, K.L., Carpenter, A.E., Finck, B.N., and Sabatini, D.M. (2011). mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell 146, 408–420.

Porstmann, T., Santos, C.R., Griffiths, B., Cully, M., Wu, M., Leevers, S., Griffiths, J.R., Chung, Y.L., and Schulze, A. (2008). SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth. Cell Metab. 8, 224–236.

Procaccini, C., Carbone, F., Di Silvestre, D., Brambilla, F., De Rosa, V., Galgani, M., Faicchia, D., Marone, G., Tramontano, D., Corona, M., et al. (2016). The Proteomic Landscape of Human Ex Vivo Regulatory and Conventional T Cells Reveals Specific Metabolic Requirements. Immunity 44, 406–421.

Qureshi, O.S., Zheng, Y., Nakamura, K., Attridge, K., Manzotti, C., Schmidt, E.M., Baker, J., Jeffery, L.E., Kaur, S., Briggs, Z., et al. (2011). Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332, 600–603.

Ramana, C.V., Chatterjee-Kishore, M., Nguyen, H., and Stark, G.R. (2000). Complex roles of Stat1 in regulating gene expression. Oncogene 19, 2619–2627.

Reck, M., Rodrı´guez-Abreu, D., Robinson, A.G., Hui, R., Csoszi, T., F } ulo € ¨ p, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al.; KEYNOTE-024 Investigators (2016). Pembrolizumab versus Chemotherapy for PD-L1- Positive Non-Small-Cell Lung Cancer. N. Engl. J. Med. 375, 1823–1833.

Rizvi, N.A., Hellmann, M.D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J.J., Lee, W., Yuan, J., Wong, P., Ho, T.S., et al. (2015). Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124–128

Robert, C., Schachter, J., Long, G.V., Arance, A., Grob, J.J., Mortier, L., Daud, A., Carlino, M.S., McNeil, C., Lotem, M., et al.; KEYNOTE-006 investigators (2015). Pembrolizumab versus Ipilimumab in Advanced Melanoma. N. Engl. J. Med. 372, 2521–2532.

Ro¨ hrig, F., and Schulze, A. (2016). The multifaceted roles of fatty acid synthesis in cancer. Nat. Rev. Cancer 16, 732–749.

Rooney, M.S., Shukla, S.A., Wu, C.J., Getz, G., and Hacohen, N. (2015). Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160, 48–61.

Sahai, E., Alberts, A.S., and Treisman, R. (1998). RhoA effector mutants reveal distinct effector pathways for cytoskeletal reorganization, SRF activation and transformation. EMBO J. 17, 1350–1361.

Saito, T., Nishikawa, H., Wada, H., Nagano, Y., Sugiyama, D., Atarashi, K., Maeda, Y., Hamaguchi, M., Ohkura, N., Sato, E., et al. (2016). Two FOXP3+ CD4+ T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat. Med. 22, 679–684.

Sato, E., Olson, S.H., Ahn, J., Bundy, B., Nishikawa, H., Qian, F., Jungbluth, A.A., Frosina, D., Gnjatic, S., Ambrosone, C., et al. (2005). Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+ /regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc. Natl. Acad. Sci. USA 102, 18538–18543.

Sauer, S., Bruno, L., Hertweck, A., Finlay, D., Leleu, M., Spivakov, M., Knight, Z.A., Cobb, B.S., Cantrell, D., O’Connor, E., et al. (2008). T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc. Natl. Acad. Sci. USA 105, 7797–7802.

Schachter, J., Ribas, A., Long, G.V., Arance, A., Grob, J.J., Mortier, L., Daud, A., Carlino, M.S., McNeil, C., Lotem, M., et al. (2017). Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet 390, 1853–1862.

Selby, M.J., Engelhardt, J.J., Quigley, M., Henning, K.A., Chen, T., Srinivasan, M., and Korman, A.J. (2013). Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol. Res. 1, 32–42.

Shitara, K., O¨ zguro € glu, M., Bang, Y.J., Di Bartolomeo, M., Mandala ` , M., Ryu, M.H., Fornaro, L., Olesinski, T., Caglevic, C., Chung, H.C., et al.; KEYNOTE- 061 investigators (2018). Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet 392, 123–133.

Simpson, T.R., Li, F., Montalvo-Ortiz, W., Sepulveda, M.A., Bergerhoff, K., Arce, F., Roddie, C., Henry, J.Y., Yagita, H., Wolchok, J.D., et al. (2013). Fcdependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J. Exp. Med. 210, 1695–1710.

Soond, D.R., Bjørgo, E., Moltu, K., Dale, V.Q., Patton, D.T., Torgersen, K.M., Galleway, F., Twomey, B., Clark, J., Gaston, J.S., et al. (2010). PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans. Blood 115, 2203–2213.

Spranger, S., Bao, R., and Gajewski, T.F. (2015). Melanoma-intrinsic b-catenin signalling prevents anti-tumour immunity. Nature 523, 231–235.

Spranger, S., Spaapen, R.M., Zha, Y., Williams, J., Meng, Y., Ha, T.T., and Gajewski, T.F. (2013). Up-regulation of PD-L1, IDO, and Tregs in the melanoma tumor microenvironment is driven by CD8+ T cells. Sci. Transl. Med. 5, 200ra116.

Subramanian, A., Tamayo, P., Mootha, V.K., Mukherjee, S., Ebert, B.L., Gillette, M.A., Paulovich, A., Pomeroy, S.L., Golub, T.R., Lander, E.S., and Mesirov, J.P. (2005). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545–15550.

Sugiyama, E., Togashi, Y., Takeuchi, Y., Shinya, S., Tada, Y., Kataoka, K., Tane, K., Sato, E., Ishii, G., Goto, K., et al. (2020). Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer. Sci. Immunol. 5, eaav3937.

Tada, Y., Togashi, Y., Kotani, D., Kuwata, T., Sato, E., Kawazoe, A., Doi, T., Wada, H., Nishikawa, H., and Shitara, K. (2018). Targeting VEGFR2 with Ramucirumab strongly impacts effector/ activated regulatory T cells and CD8+ T cells in the tumor microenvironment. J. Immunother. Cancer 6, 106.

Takeuchi, Y., Tanemura, A., Tada, Y., Katayama, I., Kumanogoh, A., and Nishikawa, H. (2018). Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma. Int. Immunol. 30, 13–22

Togashi, Y., Shitara, K., and Nishikawa, H. (2019). Regulatory T cells in cancer immunosuppression - implications for anticancer therapy. Nat. Rev. Clin. Oncol. 16, 356–371.

Tran, D.Q., Ramsey, H., and Shevach, E.M. (2007). Induction of FOXP3 expression in naive human CD4+ FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-beta dependent but does not confer a regulatory phenotype. Blood 110, 2983–2990.

Trapnell, C., Roberts, A., Goff, L., Pertea, G., Kim, D., Kelley, D.R., Pimentel, H., Salzberg, S.L., Rinn, J.L., and Pachter, L. (2012). Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 7, 562–578

Tsai, C.C., Kai, J.I., Huang, W.C., Wang, C.Y., Wang, Y., Chen, C.L., Fang, Y.T., Lin, Y.S., Anderson, R., Chen, S.H., et al. (2009). Glycogen synthase kinase-3beta facilitates IFN-gamma-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2. J Immunol. 183, 856–864.

Van Raemdonck, K., Van den Steen, P.E., Liekens, S., Van Damme, J., and Struyf, S. (2015). CXCR3 ligands in disease and therapy. Cytokine Growth Factor Rev. 26, 311–327.

Wakil, S.J. (1989). Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 28, 4523–4530.

Wang, K., Yuen, S.T., Xu, J., Lee, S.P., Yan, H.H., Shi, S.T., Siu, H.C., Deng, S., Chu, K.M., Law, S., et al. (2014). Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat. Genet. 46, 573–582.

Wang, H., Franco, F., and Ho, P.C. (2017). Metabolic Regulation of Tregs in Cancer: Opportunities for Immunotherapy. Trends Cancer 3, 583–592.

Warburg, O. (1956). On the origin of cancer cells. Science 123, 309–314.

Weber, J.S., D’Angelo, S.P., Minor, D., Hodi, F.S., Gutzmer, R., Neyns, B., Hoeller, C., Khushalani, N.I., Miller, W.H., Jr., Lao, C.D., et al. (2015). Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 16, 375–384.

Weinberg, S.E., Singer, B.D., Steinert, E.M., Martinez, C.A., Mehta, M.M., Martı´nez-Reyes, I., Gao, P., Helmin, K.A., Abdala-Valencia, H., Sena, L.A., et al. (2019). Mitochondrial complex III is essential for suppressive function of regulatory T cells. Nature 565, 495–499.

Wiig, H., Aukland, K., and Tenstad, O. (2003). Isolation of interstitial fluid from rat mammary tumors by a centrifugation method. Am. J. Physiol. Heart Circ. Physiol. 284, H416–H424.

Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., and Sakaguchi, S. (2008). CTLA-4 control over Foxp3+ regulatory T cell function. Science 322, 271–275.

Yamamoto, M., Nomura, S., Hosoi, A., Nagaoka, K., Iino, T., Yasuda, T., Saito, T., Matsushita, H., Uchida, E., Seto, Y., et al. (2018). Established gastric cancer cell lines transplantable into C57BL/6 mice show fibroblast growth factor receptor 4 promotion of tumor growth. Cancer Sci. 109, 1480–1492.

Yang, C.H., Wei, L., Pfeffer, S.R., Du, Z., Murti, A., Valentine, W.J., Zheng, Y., and Pfeffer, L.M. (2007). Identification of CXCL11 as a STAT3-dependent gene induced by IFN. J Immunol. 178, 986–992.

Yoo, H.Y., Sung, M.K., Lee, S.H., Kim, S., Lee, H., Park, S., Kim, S.C., Lee, B., Rho, K., Lee, J.E., et al. (2014). A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma. Nat. Genet. 46, 371–375.

Zumwalt, T.J., Arnold, M., Goel, A., and Boland, C.R. (2015). Active secretion of CXCL10 and CCL5 from colorectal cancer microenvironments associates with GranzymeB+ CD8+ T-cell infiltration. Oncotarget 6, 2981–2991.

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