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

Kumagai, Shogo Togashi, Yosuke Sakai, Chika Kawazoe, Akihito Kawazu, Masahito Ueno, Toshihide Sato, Eiichi Kuwata, Takeshi Kinoshita, Takahiro Yamamoto, Masami Nomura, Sachiyo Tsukamoto, Tetsuya Mano, Hiroyuki Shitara, Kohei Nishikawa, Hiroyoshi 名古屋大学

2020.07.14

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 p110delta breaks regulatory T-cell-mediated immune

tolerance to cancer. Nature 510, 407-411.

Angelin, A., Gil-de-Gomez, 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 metabolism 25, 1282-1293.e1287.

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). IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade.

The Journal of clinical investigation 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. The Journal of biological chemistry 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.

The New England journal of medicine 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). PPARgamma 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., Evdemon-Hogan, 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. Nature medicine 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 metabolism 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.

Molecular 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. Frontiers in immunology 9, 69.

Fridman, W.H., Pages, F., Sautes-Fridman, C., and Galon, J. (2012). The immune contexture in human tumours:

impact on clinical outcome. Nature reviews. 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? Nature reviews. Cancer 4,

53

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. Nature immunology 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. Journal of immunology (Baltimore, Md. : 1950) 178, 22782286.

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. Proceedings of the National Academy of Sciences of the United States of America

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. Annual review of immunology 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. Nature immunology 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. Journal of immunotherapy (Hagerstown, Md. : 1997) 28, 343351.

Ho, P.C., and Kaech, S.M. (2017). Reenergizing T cell anti-tumor immunity by harnessing immunometabolic

checkpoints and machineries. Current opinion in immunology 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. Journal of immunology (Baltimore, Md. : 1950) 184, 6833-6842.

Janku, F., Yap, T.A., and Meric-Bernstam, F. (2018). Targeting the PI3K pathway in cancer: are we making

headway? Nature reviews. Clinical oncology 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)K-p110beta 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. Nature medicine 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.

Nature genetics 46, 583-587.

Kamada, T., Togashi, Y., Tay, C., Ha, D., Sasaki, A., Nakamura, Y., Sato, E., Fukuoka, S., Tada, Y., Tanaka, A. ,

54

et al. (2019). PD-1(+) regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer.

Proceedings of the National Academy of Sciences of the United States of America.

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 (London, England) 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 biology 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.e810.

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 metabolism 29, 103-123.e105.

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. Nature reviews. Clinical oncology 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. Journal of immunology (Baltimore, Md. : 1950) 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. Journal of immunology (Baltimore, Md. : 1950) 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. Nature reviews. Immunology 17, 559-572.

55

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. Journal

of immunology (Baltimore, Md. : 1950) 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. Journal of immunology (Baltimore,

Md. : 1950) 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 discovery 6, 202216.

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

metabolism 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., Rodríguez-Abreu, D., Robinson, A.G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi,

A., Cuffe, S., et al. (2016). Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung

Cancer. The New England journal of medicine 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 nonsmall 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. (2015). Pembrolizumab versus Ipilimumab in Advanced Melanoma. The New England journal

of medicine 372, 2521-2532.

Rohrig, F., and Schulze, A. (2016). The multifaceted roles of fatty acid synthesis in cancer. Nature reviews.

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

56

cytoskeletal reorganization, SRF activation and transformation. The EMBO journal 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. Nature medicine 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. Proceedings of the National Academy of

Sciences of the United States of America 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.

Proceedings of the National Academy of Sciences of the United States of America 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 (London, England) 390, 18531862.

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 immunology research 1, 32-42.

Shitara, K., Özgüroğlu, M., Bang, Y.J., Di Bartolomeo, M., Mandalà, M., Ryu, M.H., Fornaro, L., Olesiński, T.,

Caglevic, C., Chung, H.C., et al. (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 (London, England) 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). Fc-dependent depletion of tumor-infiltrating regulatory T cells codefines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med 210, 1695-1710.

Soond, D.R., Bjorgo, 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 beta-catenin signalling prevents antitumour 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 T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Science

translational medicine 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. Proceedings of the National Academy of Sciences of

the United States of America 102, 15545-15550.

Sugiyama, E., Togashi, Y., Takeuchi, Y., Shinya, S., Tada, Y., Kataoka, K., Tane, K., Sato, E., Ishii, G., Goto, K. ,

57

et al. (2020). Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell

lung cancer. Science immunology 5.

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. Journal for immunotherapy of 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. International immunology 30, 13-22.

Togashi, Y., Shitara, K., and Nishikawa, H. (2019). Regulatory T cells in cancer immunosuppression implications for anticancer therapy. Nature reviews. Clinical oncology.

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. Nature protocols 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. Journal of immunology (Baltimore, Md. : 1950)

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 reviews 26, 311-327.

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

Wang, H., Franco, F., and Ho, P.C. (2017). Metabolic Regulation of Tregs in Cancer: Opportunities for

Immunotherapy. Trends in cancer 3, 583-592.

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. Nature genetics 46, 573-582.

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.

The Lancet. Oncology 16, 375-384.

Weinberg, S.E., Singer, B.D., Steinert, E.M., Martinez, C.A., Mehta, M.M., Martinez-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. American journal of physiology. Heart and circulatory physiology 284, H416-424.

58

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 science 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. Journal of immunology (Baltimore, Md. :

1950) 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. Nature genetics

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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