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Original Research

Intratumoral T-cell receptor repertoire composition predicts overall survival in patients with pancreatic ductal adenocarcinoma

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Article: 2320411 | Received 07 Nov 2023, Accepted 14 Feb 2024, Published online: 15 Mar 2024

References

  • O’Reilly EM, Oh D-Y, Dhani N, Renouf DJ, Lee MA, Sun W, Fisher G, Hezel A, Chang S-C, Vlahovic G. et al. Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial. JAMA Oncol. 2019;5(10):1431–14. doi:10.1001/jamaoncol.2019.1588.
  • Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(11):2913–2921. doi:10.1158/0008-5472.CAN-14-0155.
  • Balachandran VP, Łuksza M, Zhao JN, Makarov V, Moral JA, Remark R, Herbst B, Askan G, Bhanot U, Senbabaoglu Y. et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017;551(7681):512–516. doi:10.1038/nature24462.
  • Carstens JL, Correa de Sampaio P, Yang D, Barua S, Wang H, Rao A, Allison JP, LeBleu VS, Kalluri R. Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer. Nat Commun. 2017;8(1):15095. doi:10.1038/ncomms15095.
  • Aversa I, Malanga D, Fiume G, Palmieri C. Molecular T-Cell repertoire analysis as source of prognostic and predictive biomarkers for checkpoint blockade immunotherapy. Int J Mol Sci. 2020;21(7):2378. doi:10.3390/ijms21072378.
  • Bortone DS, Woodcock MG, Parker JS, Vincent BG. Improved T-cell receptor diversity estimates associate with survival and response to anti–PD-1 therapy. Cancer Immunol Res. 2021;9(1):103–112. doi:10.1158/2326-6066.CIR-20-0398.
  • Valpione S, Mundra PA, Galvani E, Campana LG, Lorigan P, De Rosa F, Gupta A, Weightman J, Mills S, Dhomen N. et al. The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival. Nat Commun. 2021;12(1):4098. doi:10.1038/s41467-021-24343-x.
  • Hogan SA, Courtier A, Cheng PF, Jaberg-Bentele NF, Goldinger SM, Manuel M, Perez S, Plantier N, Mouret J-F, Nguyen-Kim TDL. et al. Peripheral blood TCR repertoire profiling may facilitate patient stratification for immunotherapy against melanoma. Cancer Immunol Res. 2019;7(1):77–85. doi:10.1158/2326-6066.CIR-18-0136.
  • Huang H, Wang C, Rubelt F, Scriba TJ, Davis MM. Analyzing the mycobacterium tuberculosis immune response by T-cell receptor clustering with GLIPH2 and genome-wide antigen screening. Nat Biotechnol. 2020;38(10):1194–1202. doi:10.1038/s41587-020-0505-4.
  • Mayer-Blackwell K. Schattgen S, Cohen-Lavi L, Crawford, JC, Souquette A, Gaevert, JA, Hertz T, Thomas, PG, Bradley P, Fiore-Gartland A. TCR meta-clonotypes for biomarker discovery with tcrdist3: identification of public, HLA-restricted SARS-CoV-2 associated TCR features. bioRxiv. 2021;10: e68605. doi:10.7554/eLife.68605.
  • Zhang Z, Xiong D, Wang X, Liu H, Wang T. Mapping the functional landscape of T cell receptor repertoires by single-T cell transcriptomics. Nat Methods. 2021;18(1):92–99. doi:10.1038/s41592-020-01020-3.
  • Sidhom J-W, Larman HB, Pardoll DM, Baras AS. DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires. Nat Commun. 2021;12(1):1605. doi:10.1038/s41467-021-21879-w.
  • Chronister WD, Crinklaw A, Mahajan S, Vita R, Koşaloğlu-Yalçın Z, Yan Z, Greenbaum JA, Jessen LE, Nielsen M, Christley S. et al. Tcrmatch: predicting T-Cell receptor specificity based on sequence similarity to previously characterized receptors. Front Immunol. 2021;12. doi:10.3389/fimmu.2021.640725.
  • Valkiers S, Van Houcke M, Laukens K, Meysman P, Boeva DV. ClusTCR: a python interface for rapid clustering of large sets of CDR3 sequences with unknown antigen specificity. Bioinformatics. 2021;37(24):4865–4867. doi:10.1093/bioinformatics/btab446.
  • Montemurro A, Schuster V, Povlsen HR, Bentzen AK, Jurtz V, Chronister WD, Crinklaw A, Hadrup SR, Winther O, Peters B. et al. NetTCR-2.0 enables accurate prediction of TCR-peptide binding by using paired TCRα and β sequence data. Commun Biol. 2021;4(1):1060. doi:10.1038/s42003-021-02610-3.
  • Holt RA. Interpreting the T-cell receptor repertoire. Nat Biotechnol. 2017;35(9):829–830. doi:10.1038/nbt.3957.
  • Qi Q, Liu Y, Cheng Y, Glanville J, Zhang D, Lee J-Y, Olshen RA, Weyand CM, Boyd SD, Goronzy JJ. Diversity and clonal selection in the human T-cell repertoire. Proc Natl Acad Sci USA. 2014;111(36):13139–13144. doi:10.1073/pnas.1409155111.
  • Dash P, Fiore-Gartland AJ, Hertz T, Wang GC, Sharma S, Souquette A, Crawford JC, Clemens EB, Nguyen THO, Kedzierska K. et al. Quantifiable predictive features define epitope-specific T cell receptor repertoires. Nature. 2017;547(7661):89–93. doi:10.1038/nature22383.
  • Glanville J, Huang H, Nau A, Hatton O, Wagar LE, Rubelt F, Ji X, Han A, Krams SM, Pettus C. et al. Identifying specificity groups in the T cell receptor repertoire. Nature. 2017;547(7661):94–98. doi:10.1038/nature22976.
  • Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 2017;377(25):2500–2501. doi:10.1056/NEJMc1713444.
  • Seo YD, Jiang X, Sullivan KM, Jalikis FG, Smythe KS, Abbasi A, Vignali M, Park JO, Daniel SK, Pollack SM. et al. Mobilization of CD8+ T cells via CXCR4 blockade facilitates PD-1 checkpoint therapy in human pancreatic cancer. Clin Cancer Res. 2019;25(13):3934–3945. doi:10.1158/1078-0432.CCR-19-0081.
  • Thorsson V, Gibbs DL, Brown SD, Wolf D, Bortone DS, Ou Yang T-H, Porta-Pardo E, Gao GF, Plaisier CL, Eddy JA. et al. The immune landscape of cancer. Immunity. 2018;48(4):812–830.e814. doi:10.1016/j.immuni.2018.03.023.
  • Schalck A, Sakellariou-Thompson D, Forget M-A, Sei E, Hughes TG, Reuben A, Bai S, Hu M, Kumar T, Hurd MW. et al. Single-cell sequencing reveals trajectory of tumor-infiltrating lymphocyte states in pancreatic cancer. Cancer Discov. 2022;12(10):2330–2349. doi:10.1158/2159-8290.CD-21-1248.
  • Shugay M, Bagaev DV, Turchaninova MA, Bolotin DA, Britanova OV, Putintseva EV, Pogorelyy MV, Nazarov VI, Zvyagin IV, Kirgizova VI. et al. Vdjtools: unifying post-analysis of T cell receptor repertoires. PLoS Comput Biol. 2015;11(11):e1004503. doi:10.1371/journal.pcbi.1004503.
  • Amezquita RA, Lun ATL, Becht E, Carey VJ, Carpp LN, Geistlinger L, Marini F, Rue-Albrecht K, Risso D, Soneson C. et al. Orchestrating single-cell analysis with bioconductor. Nat Methods. 2020;17(2):137–145. doi:10.1038/s41592-019-0654-x.
  • McCarthy DJ, Campbell KR, Lun ATL, Wills QF, Hofacker I. Scater: pre-processing, quality control, normalization and visualization of single-cell RNA-seq data in R. Bioinformatics. 2017;33(8):1179–1186. doi:10.1093/bioinformatics/btw777.
  • Becht E, McInnes L, Healy J, Dutertre C-A, Kwok IWH, Ng LG, Ginhoux F, Newell EW. Dimensionality reduction for visualizing single-cell data using UMAP. Nat Biotechnol. 2019;37(1):38–44. doi:10.1038/nbt.4314.
  • Hafemeister C, Satija R. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol. 2019;20(1):296. doi:10.1186/s13059-019-1874-1.
  • Andreatta M, Corria-Osorio J, Müller S, Cubas R, Coukos G, Carmona SJ. Interpretation of T cell states from single-cell transcriptomics data using reference atlases. Nat Commun. 2021;12(1):2965. doi:10.1038/s41467-021-23324-4.
  • Stromnes IM, Hulbert A, Pierce RH, Greenberg PD, Hingorani SR. T-cell localization, activation, and clonal expansion in human pancreatic ductal adenocarcinoma. Cancer Immunol Res. 2017;5(11):978–991. doi:10.1158/2326-6066.CIR-16-0322.
  • Poschke I, Faryna M, Bergmann F, Flossdorf M, Lauenstein C, Hermes J, Hinz U, Hank T, Ehrenberg R, Volkmar M. et al. Identification of a tumor-reactive T-cell repertoire in the immune infiltrate of patients with resectable pancreatic ductal adenocarcinoma. Oncoimmunology. 2016;5(12):e1240859–e1240859. doi:10.1080/2162402X.2016.1240859.
  • McGranahan N, Furness AJS, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT. et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science. 2016;351(6280):1463–1469. doi:10.1126/science.aaf1490.
  • Campana LG, Mansoor W, Hill J, Macutkiewicz C, Curran F, Donnelly D, Hornung B, Charleston P, Bristow R, Lord GM. et al. T-Cell infiltration and clonality may identify distinct survival groups in colorectal cancer: development and validation of a prognostic model based on the cancer genome atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Cancers Basel. 2022;14(23):5883. doi:10.3390/cancers14235883.
  • Soto C, Bombardi RG, Kozhevnikov M, Sinkovits RS, Chen EC, Branchizio A, Kose N, Day SB, Pilkinton M, Gujral M. et al. High frequency of shared clonotypes in human T cell receptor repertoires. Cell Rep. 2020;32(2):107882. doi:10.1016/j.celrep.2020.107882.
  • Martin BD, Witten D, Willis AD. Modeling microbial abundances and dysbiosis with beta-binomial regression. Ann Appl Stat. 2020;14(1):94–115. doi:10.1214/19-AOAS1283.
  • Shang B, Liu Y, Jiang SJ, Liu Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Sci Rep. 2015;5(1):15179. doi:10.1038/srep15179.
  • Kiryu S, Ito Z, Suka M, Bito T, Kan S, Uchiyama K, Saruta M, Hata T, Takano Y, Fujioka S. et al. Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma. BMC Cancer. 2021;21(1):1197. doi:10.1186/s12885-021-08911-4.
  • Brouwer T, Ijsselsteijn M, Oosting J, Ruano D, van der Ploeg M, Dijk F, Bonsing B, Fariña A, Morreau H, Vahrmeijer A. et al. A paradoxical role for regulatory T cells in the tumor microenvironment of pancreatic cancer. Cancers Basel. 2022;14(16):3862. doi:10.3390/cancers14163862.
  • Vita R, Mahajan S, Overton JA, Dhanda SK, Martini S, Cantrell JR, Wheeler DK, Sette A, Peters B. The Immune Epitope Database (IEDB): 2018 update. Nucleic Acids Res. 2018;47(D1):D339–D343. doi:10.1093/nar/gky1006.
  • Wang Y, Sosinowski T, Novikov A, Crawford F, Neau DB, Yang J, Kwok WW, Marrack P, Kappler JW, Dai S. et al. C-terminal modification of the insulin B: 11–23 peptide creates superagonists in mouse and human type 1 diabetes. Proc Natl Acad Sci U S A. 2018;115(1):162–167. doi:10.1073/pnas.1716527115.
  • Culina S, Lalanne AI, Afonso G, Cerosaletti K, Pinto S, Sebastiani G, Kuranda K, Nigi L, Eugster A, Østerbye T. et al. Islet-reactive CD8 + T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors. Sci Immunol. 2018;3(20). doi:10.1126/sciimmunol.aao4013.
  • Shibuya KC, Goel VK, Xiong W, Sham JG, Pollack SM, Leahy AM, Whiting SH, Yeh MM, Yee C, Riddell SR. et al. Pancreatic ductal adenocarcinoma contains an effector and regulatory immune cell infiltrate that is altered by multimodal neoadjuvant treatment. PLoS One. 2014;9(5):e96565. doi:10.1371/journal.pone.0096565.
  • Jang J-E, Hajdu CH, Liot C, Miller G, Dustin ML, Bar-Sagi D. Crosstalk Between regulatory t cells and tumor-associated dendritic cells negates anti-tumor immunity in pancreatic cancer. Cell Rep. 2017;20(3):558–571. doi:10.1016/j.celrep.2017.06.062.
  • Muller M, Haghnejad V, Schaefer M, Gauchotte G, Caron B, Peyrin-Biroulet L, Bronowicki J-P, Neuzillet C, Lopez A. The immune landscape of human pancreatic ductal carcinoma: key players, clinical implications, and challenges. Cancers. 2022;14(4):995. doi:10.3390/cancers14040995.
  • Nelson CE, Thompson EA, Quarnstrom CF, Fraser KA, Seelig DM, Bhela S, Burbach BJ, Masopust D, Vezys V. Robust iterative stimulation with self-antigens overcomes CD8(+) T cell tolerance To self- and tumor antigens. Cell Rep. 2019;28(12):3092–3104.e5. doi:10.1016/j.celrep.2019.08.038.
  • Leem G, Jeon M, Kim KW, Jeong S, Choi SJ, Lee YJ, Kim E-S, Lee J-I, Ha SY, Park S-H. et al. Tumour-infiltrating bystander CD8+ T cells activated by IL-15 contribute to tumour control in non-small cell lung cancer. Thorax. 2022;77(8):769–780. doi:10.1136/thoraxjnl-2021-217001.
  • Hopkins AC, Yarchoan M, Durham JN, Yusko EC, Rytlewski JA, Robins HS, Laheru DA, Le DT, Lutz ER, Jaffee EM. et al. T cell receptor repertoire features associated with survival in immunotherapy-treated pancreatic ductal adenocarcinoma. JCI Insight. 2018;3(13). doi:10.1172/jci.insight.122092.
  • Hosoi A, Takeda K, Nagaoka K, Iino T, Matsushita H, Ueha S, Aoki S, Matsushima K, Kubo M, Morikawa T. et al. Increased diversity with reduced “diversity evenness” of tumor infiltrating T-cells for the successful cancer immunotherapy. Sci Rep. 2018;8(1):1058. doi:10.1038/s41598-018-19548-y.
  • Robert L, Tsoi J, Wang X, Emerson R, Homet B, Chodon T, Mok S, Huang RR, Cochran AJ, Comin-Anduix B. et al. CTLA4 blockade broadens the peripheral T-Cell receptor repertoire. Clin Cancer Res. 2014;20(9):2424–2432. doi:10.1158/1078-0432.CCR-13-2648.
  • Wu TD, Madireddi S, de Almeida PE, Banchereau R, Chen YJJ, Chitre AS, Chiang EY, Iftikhar H, O’Gorman WE, Au-Yeung A. et al. Peripheral T cell expansion predicts tumour infiltration and clinical response. Nature. 2020;579(7798):274–278. doi:10.1038/s41586-020-2056-8.
  • Yost KE, Satpathy AT, Wells DK, Qi Y, Wang C, Kageyama R, McNamara KL, Granja JM, Sarin KY, Brown RA. et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat Med. 2019;25(8):1251–1259. doi:10.1038/s41591-019-0522-3.