Identification of WDFY3 Neoantigens as Prognostic Markers in Longterm Survivors of Extrahepatic Cholangiocarcinoma

Author(s): Yingyi Wang, Bao Jin, Na Zhou, Zhao Sun, Jiayi Li, Qiao Chen, Xiangan Wu, Yi Zhou, Yue Shi, Xin Lu, Xinting Sang, Yilei Mao, Shunda Du*, Wenze Wang*, Chunmei Bai*

Journal Name: Current Cancer Drug Targets

Volume 20 , Issue 11 , 2020


DOI : 10.2174/1568009620999200918121456

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Graphical Abstract:


Abstract:

Background: Neoantigens are newly formed antigens that have not been previously recognized by the immune system. They may arise from altered tumor proteins that form as a result of mutations. Although neoantigens have recently been linked to antitumor immunity in long-term survivors of cancers, such as melanoma and colorectal cancer, their prognostic and immune-modulatory role in many cancer types remains undefined.

Objective: The purpose of this study is to identify prognostic markers for long-term extrahepatic cholangiocarcinoma (EHCC) survival.

Methods: We investigated neoantigens in EHCC, a rare, aggressive cancer with a 5-year overall survival rate lower than 10%, using a combination of whole-exome sequencing (WES), RNA sequencing (RNA-seq), computational biophysics, and immunohistochemistry.

Results: Our analysis revealed a decreased neutrophil infiltration-related trend of high-quality neoantigen load with IC50 <500 nM (r=-0.445, P=0.043). Among 24 EHCC patients examined, we identified four long-term survivors with WDFY3 neoantigens and none with WDFY3 neoantigens in the short-term survivors. The WDFY3 neoantigens are associated with a lower infiltration of neutrophils (p=0.013), lower expression of CCL5 (p=0.025), CXCL9 (p=0.036) and TIGIT (p=0.016), and less favorable prognosis (p=0.030). In contrast, the prognosis was not significantly associated with tumor mutation burden, neoantigen load, or immune cell infiltration.

Conclusion: We suggest that the WDFY3 neoantigens may affect prognosis by regulating antitumor immunity and that the WDFY3 neoantigens may be harnessed as potential targets for immunotherapy of EHCC.

Keywords: Extrahepatic cholangiocarcinoma, WDFY3 neoantigens, prognosis, immune cell infiltration, immune signature genes, tumor mutation burden.

[1]
Wang, L. Comparison of long-term efficacy between endoscopic and percutaneous biliary drainage for resectable extrahepatic cholangiocarcinoma with biliary obstruction: A systematic review and meta-analysis. Saudi. J. Gastroenterol.,, 2019, 25(2), 81-88.
[2]
Ma, W-J.; Wu, Z.R.; Shrestha, A.; Yang, Q.; Hu, H.J.; Wang, J.K.; Liu, F.; Zhou, R.X.; Li, Q.S.; Li, F.Y. Effectiveness of additional resection of the invasive cancer-positive proximal bile duct margin in cases of hilar cholangiocarcinoma. Hepatobiliary Surg. Nutr., 2018, 7(4), 251-269.
[http://dx.doi.org/10.21037/hbsn.2018.03.14] [PMID: 30221153]
[3]
Kim, H.; Hwang, H.; Lee, H.; Hong, H.J. L1 cell adhesion molecule promotes migration and invasion via JNK activation in extrahepatic cholangiocarcinoma cells with activating KRAS mutation. Mol. Cells, 2017, 40(5), 363-370.
[PMID: 28535665]
[4]
Ke, W.; Zeng, L.; Hu, Y.; Chen, S.; Tian, M.; Hu, Q. Detection of early-stage extrahepatic cholangiocarcinoma in patients with biliary strictures by soluble B7-H4 in the bile. Am. J. Cancer Res., 2018, 8(4), 699-707.
[PMID: 29736314]
[5]
Beal, E.W.; Tumin, D.; Moris, D.; Zhang, X.F.; Chakedis, J.; Dilhoff, M.; Schmidt, C.M.; Pawlik, T.M. Cohort contributions to trends in the incidence and mortality of intrahepatic cholangiocarcinoma. Hepatobiliary Surg. Nutr., 2018, 7(4), 270-276.
[http://dx.doi.org/10.21037/hbsn.2018.03.16] [PMID: 30221154]
[6]
Miller, A.; Asmann, Y.; Cattaneo, L.; Braggio, E.; Keats, J.; Auclair, D.; Lonial, S.; Russell, S.J.; Stewart, A.K. MMRF CoMMpass Network. High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma. Blood Cancer J., 2017, 7(9)e612
[http://dx.doi.org/10.1038/bcj.2017.94] [PMID: 28937974]
[7]
Lu, Y.C.; Robbins, P.F. Cancer immunotherapy targeting neoantigens. Semin. Immunol., 2016, 28(1), 22-27.
[http://dx.doi.org/10.1016/j.smim.2015.11.002] [PMID: 26653770]
[8]
Schumacher, T.N.; Schreiber, R.D. Neoantigens in cancer immunotherapy. Science, 2015, 348(6230), 69-74.
[http://dx.doi.org/10.1126/science.aaa4971] [PMID: 25838375]
[9]
Y, Y. Role of the tumor microenvironment in tumor progression and the clinical applications (Review). Oncology reports, 2016, 35(5), 2499-515.
[10]
Li, L.; Goedegebuure, S.P.; Gillanders, W.E. Preclinical and clinical development of neoantigen vaccines. Ann. Oncol, 2017, 28(suppl_12) xii11-xii17..
[http://dx.doi.org/10.1093/annonc/mdx681]
[11]
Chan, T.A.; Wolchok, J.D.; Snyder, A. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med., 2015, 373(20), 1984.
[http://dx.doi.org/10.1056/NEJMc1508163] [PMID: 26559592]
[12]
Van Allen, E.M.; Miao, D.; Schilling, B.; Shukla, S.A.; Blank, C.; Zimmer, L.; Sucker, A.; Hillen, U.; Foppen, M.H.G.; Goldinger, S.M.; Utikal, J.; Hassel, J.C.; Weide, B.; Kaehler, K.C.; Loquai, C.; Mohr, P.; Gutzmer, R.; Dummer, R.; Gabriel, S.; Wu, C.J.; Schadendorf, D.; Garraway, L.A. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science, 2015, 350(6257), 207-211.
[http://dx.doi.org/10.1126/science.aad0095] [PMID: 26359337]
[13]
Diaz, L.A., Jr; Le, D.T. PD-1 blockade in tumors with mismatch-repair deficiency. N. Engl. J. Med., 2015, 373(20), 1979.
[http://dx.doi.org/10.1056/NEJMc1510353] [PMID: 26559582]
[14]
Sahin, U.; Derhovanessian, E.; Miller, M.; Kloke, B.P.; Simon, P.; Löwer, M.; Bukur, V.; Tadmor, A.D.; Luxemburger, U.; Schrörs, B.; Omokoko, T.; Vormehr, M.; Albrecht, C.; Paruzynski, A.; Kuhn, A.N.; Buck, J.; Heesch, S.; Schreeb, K.H.; Müller, F.; Ortseifer, I.; Vogler, I.; Godehardt, E.; Attig, S.; Rae, R.; Breitkreuz, A.; Tolliver, C.; Suchan, M.; Martic, G.; Hohberger, A.; Sorn, P.; Diekmann, J.; Ciesla, J.; Waksmann, O.; Brück, A.K.; Witt, M.; Zillgen, M.; Rothermel, A.; Kasemann, B.; Langer, D.; Bolte, S.; Diken, M.; Kreiter, S.; Nemecek, R.; Gebhardt, C.; Grabbe, S.; Höller, C.; Utikal, J.; Huber, C.; Loquai, C.; Türeci, Ö. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature, 2017, 547(7662), 222-226.
[http://dx.doi.org/10.1038/nature23003] [PMID: 28678784]
[15]
Liu, C.J.; Schaettler, M.; Blaha, D.T.; Bowman-Kirigin, J.A.; Kobayashi, D.K.; Livingstone, A.J.; Bender, D.; Miller, C.A.; Kranz, D.M.; Johanns, T.M.; Dunn, G.P. Treatment of an aggressive orthotopic murine glioblastoma model with combination checkpoint blockade and a multivalent neoantigen vaccine. Neuro-oncol., 2020.noaa050
[http://dx.doi.org/10.1093/neuonc/noaa050] [PMID: 32133512]
[16]
K, H. Mutational burden and signatures in 4000 Japanese cancers provide insights into tumorigenesis and response to therapy. Cancer science, 2019, 110(8), 2620-2628.
[17]
JM, D. Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal connectivity in the mammalian brain. eLife; , 2016, 5, . (undefined)
[18]
Tsai, T.L.; Wang, H.C.; Hung, C.H.; Lin, P.C.; Lee, Y.S.; Chen, H.H.W.; Su, W.C. Wheat germ agglutinin-induced paraptosis-like cell death and protective autophagy is mediated by autophagy-linked FYVE inhibition. Oncotarget, 2017, 8(53), 91209-91222.
[http://dx.doi.org/10.18632/oncotarget.20436] [PMID: 29207637]
[19]
Hilf, N.; Kuttruff-Coqui, S.; Frenzel, K.; Bukur, V.; Stevanović, S.; Gouttefangeas, C.; Platten, M.; Tabatabai, G.; Dutoit, V.; van der Burg, S.H.; Thor Straten, P.; Martínez-Ricarte, F.; Ponsati, B.; Okada, H.; Lassen, U.; Admon, A.; Ottensmeier, C.H.; Ulges, A.; Kreiter, S.; von Deimling, A.; Skardelly, M.; Migliorini, D.; Kroep, J.R.; Idorn, M.; Rodon, J.; Piró, J.; Poulsen, H.S.; Shraibman, B.; McCann, K.; Mendrzyk, R.; Löwer, M.; Stieglbauer, M.; Britten, C.M.; Capper, D.; Welters, M.J.P.; Sahuquillo, J.; Kiesel, K.; Derhovanessian, E.; Rusch, E.; Bunse, L.; Song, C.; Heesch, S.; Wagner, C.; Kemmer-Brück, A.; Ludwig, J.; Castle, J.C.; Schoor, O.; Tadmor, A.D.; Green, E.; Fritsche, J.; Meyer, M.; Pawlowski, N.; Dorner, S.; Hoffgaard, F.; Rössler, B.; Maurer, D.; Weinschenk, T.; Reinhardt, C.; Huber, C.; Rammensee, H.G.; Singh-Jasuja, H.; Sahin, U.; Dietrich, P.Y.; Wick, W. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature, 2019, 565(7738), 240-245.
[http://dx.doi.org/10.1038/s41586-018-0810-y] [PMID: 30568303]
[20]
Ott, P.A.; Hu, Z.; Keskin, D.B.; Shukla, S.A.; Sun, J.; Bozym, D.J.; Zhang, W.; Luoma, A.; Giobbie-Hurder, A.; Peter, L.; Chen, C.; Olive, O.; Carter, T.A.; Li, S.; Lieb, D.J.; Eisenhaure, T.; Gjini, E.; Stevens, J.; Lane, W.J.; Javeri, I.; Nellaiappan, K.; Salazar, A.M.; Daley, H.; Seaman, M.; Buchbinder, E.I.; Yoon, C.H.; Harden, M.; Lennon, N.; Gabriel, S.; Rodig, S.J.; Barouch, D.H.; Aster, J.C.; Getz, G.; Wucherpfennig, K.; Neuberg, D.; Ritz, J.; Lander, E.S.; Fritsch, E.F.; Hacohen, N.; Wu, C.J. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature, 2017, 547(7662), 217-221.
[http://dx.doi.org/10.1038/nature22991] [PMID: 28678778]
[21]
Balachandran, V.P.; Łuksza, M.; Zhao, J.N.; Makarov, V.; Moral, J.A.; Remark, R.; Herbst, B.; Askan, G.; Bhanot, U.; Senbabaoglu, Y.; Wells, D.K.; Cary, C.I.O.; Grbovic-Huezo, O.; Attiyeh, M.; Medina, B.; Zhang, J.; Loo, J.; Saglimbeni, J.; Abu-Akeel, M.; Zappasodi, R.; Riaz, N.; Smoragiewicz, M.; Kelley, Z.L.; Basturk, O.; Gönen, M.; Levine, A.J.; Allen, P.J.; Fearon, D.T.; Merad, M.; Gnjatic, S.; Iacobuzio-Donahue, C.A.; Wolchok, J.D.; DeMatteo, R.P.; Chan, T.A.; Greenbaum, B.D.; Merghoub, T.; Leach, S.D. Australian Pancreatic Cancer Genome Initiative; Garvan Institute of Medical Research; Prince of Wales Hospital; Royal North Shore Hospital; University of Glasgow; St Vincent’s Hospital; QIMR Berghofer Medical Research Institute; University of Melbourne, Centre for Cancer Research; University of Queensland, Institute for Molecular Bioscience; Bankstown Hospital; Liverpool Hospital; Royal Prince Alfred Hospital, Chris O’Brien Lifehouse; Westmead Hospital; Fremantle Hospital; St John of God Healthcare; Royal Adelaide Hospital; Flinders Medical Centre; Envoi Pathology; Princess Alexandria Hospital; Austin Hospital; Johns Hopkins Medical Institutes; ARC-Net Centre for Applied Research on Cancer. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature, 2017, 551(7681), 512-516.
[http://dx.doi.org/10.1038/nature24462] [PMID: 29132146]
[22]
Keskin, D.B.; Anandappa, A.J.; Sun, J.; Tirosh, I.; Mathewson, N.D.; Li, S.; Oliveira, G.; Giobbie-Hurder, A.; Felt, K.; Gjini, E.; Shukla, S.A.; Hu, Z.; Li, L.; Le, P.M.; Allesøe, R.L.; Richman, A.R.; Kowalczyk, M.S.; Abdelrahman, S.; Geduldig, J.E.; Charbonneau, S.; Pelton, K.; Iorgulescu, J.B.; Elagina, L.; Zhang, W.; Olive, O.; McCluskey, C.; Olsen, L.R.; Stevens, J.; Lane, W.J.; Salazar, A.M.; Daley, H.; Wen, P.Y.; Chiocca, E.A.; Harden, M.; Lennon, N.J.; Gabriel, S.; Getz, G.; Lander, E.S.; Regev, A.; Ritz, J.; Neuberg, D.; Rodig, S.J.; Ligon, K.L.; Suvà, M.L.; Wucherpfennig, K.W.; Hacohen, N.; Fritsch, E.F.; Livak, K.J.; Ott, P.A.; Wu, C.J.; Reardon, D.A. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature, 2019, 565(7738), 234-239.
[http://dx.doi.org/10.1038/s41586-018-0792-9] [PMID: 30568305]
[23]
Jurtz, V.; Paul, S.; Andreatta, M.; Marcatili, P.; Peters, B.; Nielsen, M. NetMHCpan-4.0: Improved peptide-MHC class I interaction predictions integrating eluted ligand and peptide binding affinity data. J. Immunol., 2017, 199(9), 3360-3368.
[http://dx.doi.org/10.4049/jimmunol.1700893] [PMID: 28978689]
[24]
S, K. PI3K/AKT pathway genetic alterations and dysregulation of expression in bladder cancer. J. of B.U.ON., 2019, 24(1), 329-337.
[25]
S, K. PI3K/AKT pathway genetic alterations and dysregulation of expression in bladder cancer. J. of B.U.ON., 2018, 24(1), 329-337.
[26]
Guo, D. Exosomes from heat-stressed tumor cells inhibit tumor growth by converting regulatory T cells to Th17 cells via IL-6. Immunology, 2018.
[http://dx.doi.org/10.1111/imm.12874]
[27]
Lin, J.; Long, J.; Wan, X.; Chen, J.; Bai, Y.; Wang, A.; Yang, X.; Wu, Y.; Robson, S.C.; Sang, X.; Zhao, H. Classification of gallbladder cancer by assessment of CD8+ TIL and PD-L1 expression. BMC Cancer, 2018, 18(1), 766.
[http://dx.doi.org/10.1186/s12885-018-4651-8] [PMID: 30055582]
[28]
Matsushita, H.; Sato, Y.; Karasaki, T.; Nakagawa, T.; Kume, H.; Ogawa, S.; Homma, Y.; Kakimi, K. Neoantigen load, antigen presentation machinery, and immune signatures determine prognosis in clear cell renal cell carcinoma. Cancer Immunol. Res., 2016, 4(5), 463-471.
[http://dx.doi.org/10.1158/2326-6066.CIR-15-0225] [PMID: 26980598]
[29]
Goodman, A.M.; Kato, S.; Bazhenova, L.; Patel, S.P.; Frampton, G.M.; Miller, V.; Stephens, P.J.; Daniels, G.A.; Kurzrock, R. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol. Cancer Ther., 2017, 16(11), 2598-2608.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0386] [PMID: 28835386]
[30]
Devarakonda, S.; Rotolo, F.; Tsao, M.S.; Lanc, I.; Brambilla, E.; Masood, A.; Olaussen, K.A.; Fulton, R.; Sakashita, S.; McLeer-Florin, A.; Ding, K.; Le Teuff, G.; Shepherd, F.A.; Pignon, J.P.; Graziano, S.L.; Kratzke, R.; Soria, J.C.; Seymour, L.; Govindan, R.; Michiels, S. Tumor mutation burden as a biomarker in resected non-small-cell lung cancer. J. Clin. Oncol., 2018, 36(30), 2995-3006.
[http://dx.doi.org/10.1200/JCO.2018.78.1963] [PMID: 30106638]
[31]
Duperret, E.K.; Perales-Puchalt, A.; Stoltz, R.; G H, H.; Mandloi, N.; Barlow, J.; Chaudhuri, A.; Sardesai, N.Y.; Weiner, D.B. A synthetic DNA, multi-neoantigen vaccine drives predominately MHC class I CD8+ T-cell responses, impacting tumor challenge. Cancer Immunol. Res., 2019, 7(2), 174-182.
[http://dx.doi.org/10.1158/2326-6066.CIR-18-0283] [PMID: 30679156]
[32]
Teo, M.Y.; Seier, K.; Ostrovnaya, I.; Regazzi, A.M.; Kania, B.E.; Moran, M.M.; Cipolla, C.K.; Bluth, M.J.; Chaim, J.; Al-Ahmadie, H.; Snyder, A.; Carlo, M.I.; Solit, D.B.; Berger, M.F.; Funt, S.; Wolchok, J.D.; Iyer, G.; Bajorin, D.F.; Callahan, M.K.; Rosenberg, J.E. Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1/PD-L1 blockade in advanced urothelial cancers. J. Clin. Oncol., 2018, 36(17), 1685-1694.
[http://dx.doi.org/10.1200/JCO.2017.75.7740] [PMID: 29489427]
[33]
Rowson-Hodel, A.R.; Wald, J.H.; Hatakeyama, J.; O’Neal, W.K.; Stonebraker, J.R.; VanderVorst, K.; Saldana, M.J.; Borowsky, A.D.; Sweeney, C.; Carraway, K.L., III Membrane Mucin Muc4 promotes blood cell association with tumor cells and mediates efficient metastasis in a mouse model of breast cancer. Oncogene, 2018, 37(2), 197-207.
[http://dx.doi.org/10.1038/onc.2017.327] [PMID: 28892049]
[34]
F, K. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations. J. Immunother. Cancer., 2018, 6(1), 141.
[35]
Schläfli, A.M.; Isakson, P.; Garattini, E.; Simonsen, A.; Tschan, M.P. The autophagy scaffold protein ALFY is critical for the granulocytic differentiation of AML cells. Sci. Rep., 2017, 7(1), 12980.
[http://dx.doi.org/10.1038/s41598-017-12734-4] [PMID: 29021535]
[36]
Q, Z. LncRNA WDFY3-AS2 suppresses proliferation and invasion in oesophageal squamous cell carcinoma by regulating miR-2355-5p/SOCS2 axis. J. cell. mol. med., 2020.
[37]
Kim, Y.; Lee, D.; Lee, J.; Lee, S.; Lawler, S. Role of tumor-associated neutrophils in regulation of tumor growth in lung cancer development: A mathematical model. PLoS One, 2019, 14(1), e0211041.
[http://dx.doi.org/10.1371/journal.pone.0211041] [PMID: 30689655]
[38]
Saha, S.; Biswas, S.K. Tumor-associated neutrophils show phenotypic and functional divergence in human lung cancer. Cancer Cell, 2016, 30(1), 11-13.
[http://dx.doi.org/10.1016/j.ccell.2016.06.016] [PMID: 27411583]
[39]
Gregory, A.D.; Houghton, A.M. Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res., 2011, 71(7), 2411-2416.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2583] [PMID: 21427354]
[40]
Spano, D.; Zollo, M. Immune Cells Within the Tumor Microenvironment.Interaction of Immune and Cancer Cells; Klink, M., Ed.; Springer Vienna: Vienna, 2014, pp. 1-23.
[http://dx.doi.org/10.1007/978-3-7091-1300-4_1]
[41]
Fujita, T.; Matsuoka, T.; Honda, T.; Kabashima, K.; Hirata, T.; Narumiya, S. A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J. Invest. Dermatol., 2011, 131(8), 1660-1667.
[http://dx.doi.org/10.1038/jid.2011.123] [PMID: 21593768]
[42]
Ochiai, E.; Sa, Q.; Brogli, M.; Kudo, T.; Wang, X.; Dubey, J.P.; Suzuki, Y. CXCL9 is important for recruiting immune T cells into the brain and inducing an accumulation of the T cells to the areas of tachyzoite proliferation to prevent reactivation of chronic cerebral infection with Toxoplasma gondii. Am. J. Pathol., 2015, 185(2), 314-324.
[http://dx.doi.org/10.1016/j.ajpath.2014.10.003] [PMID: 25432064]
[43]
You, Y.; Li, Y.; Li, M.; Lei, M.; Wu, M.; Qu, Y.; Yuan, Y.; Chen, T.; Jiang, H. Ovarian cancer stem cells promote tumour immune privilege and invasion via CCL5 and regulatory T cells. Clin. Exp. Immunol., 2018, 191(1), 60-73.
[http://dx.doi.org/10.1111/cei.13044] [PMID: 28868628]
[44]
Tan, S.; Wang, K.; Sun, F.; Li, Y.; Gao, Y. CXCL9 promotes prostate cancer progression through inhibition of cytokines from T cells. Mol. Med. Rep., 2018, 18(2), 1305-1310.
[http://dx.doi.org/10.3892/mmr.2018.9152] [PMID: 29901197]
[45]
Hwaiz, R.; Rahman, M.; Syk, I.; Zhang, E.; Thorlacius, H. Rac1-dependent secretion of platelet-derived CCL5 regulates neutrophil recruitment via activation of alveolar macrophages in septic lung injury. J. Leukoc. Biol., 2015, 97(5), 975-984.
[http://dx.doi.org/10.1189/jlb.4A1214-603R] [PMID: 25717148]
[46]
Boff, D.; Crijns, H.; Janssens, R.; Vanheule, V.; Menezes, G.B.; Macari, S.; Silva, T.A.; Amaral, F.A.; Proost, P. The chemokine fragment CXCL9(74-103) diminishes neutrophil recruitment and joint inflammation in antigen-induced arthritis. J. Leukoc. Biol., 2018, 104(2), 413-422.
[http://dx.doi.org/10.1002/JLB.3MA1217-502R] [PMID: 29733455]
[47]
Zhou, X.M.; Li, W.Q.; Wu, Y.H.; Han, L.; Cao, X.G.; Yang, X.M.; Wang, H.F.; Zhao, W.S.; Zhai, W.J.; Qi, Y.M.; Gao, Y.F. Intrinsic Expression of Immune Checkpoint Molecule TIGIT Could Help Tumor Growth in vivo by Suppressing the Function of NK and CD8+ T Cells. Front. Immunol., 2018, 9, 2821.
[http://dx.doi.org/10.3389/fimmu.2018.02821] [PMID: 30555485]
[48]
He, W.; Zhang, H.; Han, F.; Chen, X.; Lin, R.; Wang, W.; Qiu, H.; Zhuang, Z.; Liao, Q.; Zhang, W.; Cai, Q.; Cui, Y.; Jiang, W.; Wang, H.; Ke, Z. CD155T/TIGIT signaling regulates CD8+ t-cell metabolism and promotes tumor progression in human gastric cancer. Cancer Res., 2017, 77(22), 6375-6388.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0381] [PMID: 28883004]
[49]
Wang, X.; Li, M. Correlate tumor mutation burden with immune signatures in human cancers. BMC Immunol., 2019, 20(1), 4.
[http://dx.doi.org/10.1186/s12865-018-0285-5] [PMID: 30634925]
[50]
Y,, O.-O. Prognostic Impact of Tumor Mutation Burden in Patients With Completely Resected Non-Small Cell Lung Cancer: Brief Report. J. Thoracic Oncol. , 2018, 13(8), 1217-1221.


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VOLUME: 20
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Year: 2020
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DOI: 10.2174/1568009620999200918121456
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