Phased differentiation of γδ T and T CD8 tumor-infiltrating lymphocytes revealed by single-cell transcriptomics of human cancers

References

• Dieli F, Poccia F, Lipp M, Sireci G, Caccamo N, Di Sano C, Salerno A. Differentiation of effector/memory Vdelta2 T cells and migratory routes in lymph nodes or inflammatory sites. J Exp Med. 2003;198(3):391–14. doi:10.1084/jem.20030235.
   PubMed Web of Science ®Google Scholar
• Hayday AC, Vantourout P. The innate biologies of adaptive antigen receptors. Annu Rev Immunol. 2020;38(1):487–510. doi:10.1146/annurev-immunol-102819-023144.
   PubMed Web of Science ®Google Scholar
• Sebestyen Z, Prinz I, Dechanet-Merville J, Silva-Santos B, Kuball J. Translating gammadelta (gammadelta) T cells and their receptors into cancer cell therapies. Nat Rev Drug Discov. 2020;19(3):169–184. doi:10.1038/s41573-019-0038-z.
   PubMed Web of Science ®Google Scholar
• Tosolini M, Pont F, Poupot M, Vergez F, Nicolau-Travers ML, Vermijlen D, Sarry JE, Dieli F, Fournie JJ. Assessment of tumor-infiltrating TCRVγ9Vδ2γδlymphocyte abundance by deconvolution of human cancers microarrays. Oncoimmunology. 2017;6(3):e1284723. doi:10.1080/2162402X.2017.1284723.
   PubMed Web of Science ®Google Scholar
• Meraviglia S, Lo Presti E, Tosolini M, La Mendola C, Orlando V, Todaro M, Catalano V, Stassi G, Cicero G, Vieni S, et al. Distinctive features of tumor-infiltrating gammadelta T lymphocytes in human colorectal cancer. Oncoimmunology. 2017;6(10):e1347742. doi:10.1080/2162402X.2017.1347742.
   PubMed Web of Science ®Google Scholar
• Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, Nair VS, Xu Y, Khuong A, Hoang CD, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21(8):938–945. doi:10.1038/nm.3909.
   PubMed Web of Science ®Google Scholar
• Wu Y, Kyle-Cezar F, Woolf RT, Naceur-Lombardelli C, Owen J, Biswas D, Lorenc A, Vantourout P, Gazinska P, Grigoriadis A, et al. An innate-like Vδ1+γδ T cell compartment in the human breast is associated with remission in triple-negative breast cancer. Sci Transl Med. 2019;11(513):eaax9364. doi:10.1126/scitranslmed.aax9364.
   PubMed Web of Science ®Google Scholar
• Mikulak J, Oriolo F, Bruni E, Roberto A, Colombo FS, Villa A, Bosticardo M, Bortolomai I, Lo Presti E, Meraviglia S, et al. NKp46-expressing human gut-resident intraepithelial Vdelta1 T cell subpopulation exhibits high antitumor activity against colorectal cancer. JCI Insight. 2019;4(24). doi:10.1172/jci.insight.125884.
   PubMed Web of Science ®Google Scholar
• Foord E, Arruda LCM, Gaballa A, Klynning C, Uhlin M. Characterization of ascites- and tumor-infiltrating gammadelta T cells reveals distinct repertoires and a beneficial role in ovarian cancer. Sci Transl Med. 2021;13(577):eabb0192. doi:10.1126/scitranslmed.abb0192.
   PubMed Web of Science ®Google Scholar
• Pizzolato G, Kaminski H, Tosolini M, Franchini DM, Pont F, Martins F, Valle C, Labourdette D, Cadot S, Quillet-Mary A, et al. Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVdelta1 and TCRVdelta2 gammadelta T lymphocytes. Proc Natl Acad Sci U S A. 2019;116(24):11906–11915. doi:10.1073/pnas.1818488116.
   PubMed Web of Science ®Google Scholar
• Girard JP, Moussion C, Forster R. HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes. Nat Rev Immunol. 2012;12(11):762–773. doi:10.1038/nri3298.
   PubMed Web of Science ®Google Scholar
• Zhou X, Yu S, Zhao DM, Harty JT, Badovinac VP, Xue HH. Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity. 2010;33(2):229–240. doi:10.1016/j.immuni.2010.08.002.
   PubMed Web of Science ®Google Scholar
• Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004;22(1):745–763. doi:10.1146/annurev.immunol.22.012703.104702.
   PubMed Web of Science ®Google Scholar
• Restifo NP, Gattinoni L. Lineage relationship of effector and memory T cells. Curr Opin Immunol. 2013;25(5):556–563. doi:10.1016/j.coi.2013.09.003.
   PubMed Web of Science ®Google Scholar
• Angelini DF, Borsellino G, Poupot M, Diamantini A, Poupot R, Bernardi G, Poccia F, Fournie JJ, Battistini L. FcgammaRIII discriminates between two subsets of Vgamma9Vdelta2 effector cells with different responses and activation pathways. Blood. 2004;104(6):1801–1807. doi:10.1182/blood-2004-01-0331.
   PubMed Web of Science ®Google Scholar
• Khan O, Giles JR, McDonald S, Manne S, Ngiow SF, Patel KP, Werner MT, Huang AC, Alexander KA, Wu JE, et al. TOX transcriptionally and epigenetically programs CD8(+) T cell exhaustion. Nature. 2019;571(7764):211–218. doi:10.1038/s41586-019-1325-x.
   PubMed Web of Science ®Google Scholar
• Gattinoni L, Speiser DE, Lichterfeld M, Bonini C. T memory stem cells in health and disease. Nat Med. 2017;23(1):18–27. doi:10.1038/nm.4241.
   PubMed Web of Science ®Google Scholar
• Galletti G, De Simone G, Mazza EMC, Puccio S, Mezzanotte C, Bi TM, Davydov AN, Metsger M, Scamardella E, Alvisi G, et al. Two subsets of stem-like CD8(+) memory T cell progenitors with distinct fate commitments in humans. Nat Immunol. 2020;21(12):1552–1562. doi:10.1038/s41590-020-0791-5.
   PubMed Web of Science ®Google Scholar
• Pont F, Tosolini M, Gao Q, Perrier M, Madrid-Mencia M, Huang TS, Neuvial P, Ayyoub M, Nazor K, Fournie JJ. Single-cell virtual cytometer allows user-friendly and versatile analysis and visualization of multimodal single cell RNAseq datasets. NAR Genom Bioinform. 2020;2(2):lqaa025. doi:10.1093/nargab/lqaa025.
   PubMedGoogle Scholar
• Wu TD, Madireddi S, De Almeida PE, Banchereau R, Chen YJ, 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.
   PubMed Web of Science ®Google Scholar
• Fairfax BP, Taylor CA, Watson RA, Nassiri I, Danielli S, Fang H, Mahe EA, Cooper R, Woodcock V, Traill Z, et al. Peripheral CD8(+) T cell characteristics associated with durable responses to immune checkpoint blockade in patients with metastatic melanoma. Nat Med. 2020;26(2):193–199. doi:10.1038/s41591-019-0734-6.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Balanca CC, Scarlata CM, Michelas M, Devaud C, Sarradin V, Franchet C, Martinez Gomez C, Gomez-Roca C, Tosolini M, Heaugwane D, et al. Dual relief of T-lymphocyte proliferation and effector function underlies response to PD-1 blockade in epithelial malignancies. Cancer Immunol Res. 2020;8(7):869–882. doi:10.1158/2326-6066.CIR-19-0855.
   PubMed Web of Science ®Google Scholar
• Sade-Feldman M, Yizhak K, Bjorgaard SL, Ray JP, De Boer CG, Jenkins RW, Lieb DJ, Chen JH, Frederick DT, Barzily-Rokni M, et al. Defining T cell states associated with response to checkpoint immunotherapy in melanoma. Cell. 2018;175(4):998–1013e1020. doi:10.1016/j.cell.2018.10.038.
   PubMed Web of Science ®Google Scholar
• Caccamo N, Meraviglia S, Ferlazzo V, Angelini D, Borsellino G, Poccia F, Battistini L, Dieli F, Salerno A. Differential requirements for antigen or homeostatic cytokines for proliferation and differentiation of human Vgamma9Vdelta2 naive, memory and effector T cell subsets. Eur J Immunol. 2005;35(6):1764–1772. doi:10.1002/eji.200525983.
   PubMed Web of Science ®Google Scholar
• Alpert A, Moore LS, Dubovik T, Shen-Orr SS. Alignment of single-cell trajectories to compare cellular expression dynamics. Nat Methods. 2018;15(4):267–270. doi:10.1038/nmeth.4628.
   PubMed Web of Science ®Google Scholar
• Trapnell C, Cacchiarelli D, Grimsby J, Pokharel P, Li S, Morse M, Lennon NJ, Livak KJ, Mikkelsen TS, Rinn JL. The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells. Nat Biotechnol. 2014;32(4):381–386. doi:10.1038/nbt.2859.
   PubMed Web of Science ®Google Scholar
• Van Den Berge K, Roux De Bézieux H, Street K, Saelens W, Cannoodt R, Saeys Y, Dudoit S, Clement L. Trajectory-based differential expression analysis for single-cell sequencing data. Nat Commun. 2020;11(1):1201. doi:10.1038/s41467-020-14766-3.
   PubMed Web of Science ®Google Scholar
• Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, Hao Y, Stoeckius M, Smibert P, Satija R. Comprehensive integration of single-cell data. Cell. 2019;177(7):1888–1902e1821. doi:10.1016/j.cell.2019.05.031.
   PubMed Web of Science ®Google Scholar
• Fiala GJ, Gomes AQ, Silva-Santos B. From thymus to periphery: molecular basis of effector gammadelta-T cell differentiation. Immunol Rev. 2020;298(1):47–60. doi:10.1111/imr.12918.
   PubMed Web of Science ®Google Scholar
• Di Marco R, Roberts NA, Dart RJ, Vantourout P, Jandke A, Nussbaumer O, Deban L, Cipolat S, Hart R, Iannitto ML. Epithelia use butyrophilin-like molecules to shape organ-specific gammadelta T cell compartments. Cell. 2016;167(1):203–218 e217. doi:10.1016/j.cell.2016.08.030.
   PubMed Web of Science ®Google Scholar
• Savas P, Virassamy B, Ye C, Salim A, Mintoff CP, Caramia F, Salgado R, Byrne DJ, Teo ZL, Dushyanthen S, et al. Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis. Nat Med. 2018;24(7):986–993. doi:10.1038/s41591-018-0078-7.
   PubMed Web of Science ®Google Scholar
• Simoni Y, Becht E, Fehlings M, Loh CY, Koo SL, Teng KWW, Yeong JPS, Nahar R, Zhang T, Kared H, et al. Bystander CD8(+) T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature. 2018;557(7706):575–579. doi:10.1038/s41586-018-0130-2.
   PubMed Web of Science ®Google Scholar
• Hewavisenti R, Ferguson A, Wang K, Jones D, Gebhardt T, Edwards J, Zhang M, Britton W, Yang J, Hong A, et al. CD103+ tumor-resident CD8+ T cell numbers underlie improved patient survival in oropharyngeal squamous cell carcinoma. J Immunother Cancer. 2020;8(1):e000452. doi:10.1136/jitc-2019-000452.
   PubMed Web of Science ®Google Scholar
• Challenor S, Tucker D. SARS-CoV-2-induced remission of Hodgkin lymphoma. Br J Haematol. 2021;192(3):415. doi:10.1111/bjh.17116.
   PubMed Web of Science ®Google Scholar
• Couzi L, Levaillant Y, Jamai A, Pitard V, Lassalle R, Martin K, Garrigue I, Hawchar O, Siberchicot F, Moore N, et al. Cytomegalovirus-induced gammadelta T cells associate with reduced cancer risk after kidney transplantation. J Am Soc Nephrol. 2010;21(1):181–188. doi:10.1681/ASN.2008101072.
   PubMed Web of Science ®Google Scholar
• Payne KK, Mine JA, Biswas S, Chaurio RA, Perales-Puchalt A, Anadon CM, Costich TL, Harro CM, Walrath J, Ming Q, et al. BTN3A1 governs antitumor responses by coordinating alphabeta and gammadelta T cells. Science. 2020;369(6506):942–949. doi:10.1126/science.aay2767.
   PubMed Web of Science ®Google Scholar
• Fournie JJ, Bonneville M. Stimulation of gamma delta T cells by phosphoantigens. Res Immunol. 1996;147(5):338–347. doi:10.1016/0923-2494(96)89648-9.
   PubMedGoogle Scholar
• Dechanet J, Merville P, Lim A, Retiere C, Pitard V, Lafarge X, Michelson S, Meric C, Hallet MM, Kourilsky P, et al. Implication of gammadelta T cells in the human immune response to cytomegalovirus. J Clin Invest. 1999;103(10):1437–1449. doi:10.1172/JCI5409.
   PubMed Web of Science ®Google Scholar
• Marlin R, Pappalardo A, Kaminski H, Willcox CR, Pitard V, Netzer S, Khairallah C, Lomenech AM, Harly C, Bonneville M, et al. Sensing of cell stress by human gammadelta TCR-dependent recognition of annexin A2. Proc Natl Acad Sci U S A. 2017;114(12):3163–3168. doi:10.1073/pnas.1621052114.
   PubMed Web of Science ®Google Scholar
• Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–571. doi:10.1038/nature13954.
   PubMed Web of Science ®Google Scholar
• Daud AI, Loo K, Pauli ML, Sanchez-Rodriguez R, Sandoval PM, Taravati K, Tsai K, Nosrati A, Nardo L, Alvarado MD, et al. Tumor immune profiling predicts response to anti-PD-1 therapy in human melanoma. J Clin Invest. 2016;126(9):3447–3452. doi:10.1172/JCI87324.
   PubMed Web of Science ®Google Scholar
• Riaz N, Havel JJ, Makarov V, Desrichard A, Urba WJ, Sims JS, Hodi FS, Martin-Algarra S, Mandal R, Sharfman WH, et al. Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell. 2017;171(4):934–949e916. doi:10.1016/j.cell.2017.09.028.
   PubMed Web of Science ®Google Scholar
• Prat A, Navarro A, Pare L, Reguart N, Galvan P, Pascual T, Martinez A, Nuciforo P, Comerma L, Alos L, et al. Immune-related gene expression profiling after PD-1 blockade in non-small cell lung carcinoma, head and neck squamous cell carcinoma, and melanoma. Cancer Res. 2017;77(13):3540–3550. doi:10.1158/0008-5472.CAN-16-3556.
   PubMed Web of Science ®Google Scholar
• Efremova M, Rieder D, Klepsch V, Charoentong P, Finotello F, Hackl H, Hermann-Kleiter N, Lower M, Baier G, Krogsdam A, et al. Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution. Nat Commun. 2018;9(1):32. doi:10.1038/s41467-017-02424-0.
   PubMed Web of Science ®Google Scholar
• Patel SJ, Sanjana NE, Kishton RJ, Eidizadeh A, Vodnala SK, Cam M, Gartner JJ, Jia L, Steinberg SM, Yamamoto TN, et al. Identification of essential genes for cancer immunotherapy. Nature. 2017;548(7669):537–542. doi:10.1038/nature23477.
   PubMed Web of Science ®Google Scholar
• Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321–330. doi:10.1038/nature21349.
   PubMed Web of Science ®Google Scholar
• Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36(5):411–420. doi:10.1038/nbt.4096.
   PubMed Web of Science ®Google Scholar
• Van Der Maaten LJP, Hinton GE. Visualizing high-dimensional data using t-SNE. J Mach Learn Res. 2008;9:2579–2605.
   Web of Science ®Google Scholar
• McInnes L, Healy J, Melville J. Umap: Uniform manifold approximation and projection for dimension reduction. ArXiv. 2018. arXiv:1802.03426.
   Google Scholar
• Pont F, Tosolini M, Fournie JJ. Single-cell signature explorer for comprehensive visualization of single cell signatures across scRNA-seq datasets. Nucleic Acids Res. 2019;47(21):e133. doi:10.1093/nar/gkz601.
   PubMed Web of Science ®Google Scholar
• Stoeckius M, Hafemeister C, Stephenson W, Houck-Loomis B, Chattopadhyay PK, Swerdlow H, Satija R, Smibert P. Simultaneous epitope and transcriptome measurement in single cells. Nat Methods. 2017;14(9):865–868. doi:10.1038/nmeth.4380.
   PubMed Web of Science ®Google Scholar
• Gaydosik AM, Tabib T, Geskin LJ, Bayan CA, Conway JF, Lafyatis R, Fuschiotti P. Single-cell lymphocyte heterogeneity in advanced cutaneous T-cell lymphoma skin tumors. Clin Cancer Res. 2019;25(14):4443–4454. doi:10.1158/1078-0432.CCR-19-0148.
   PubMed Web of Science ®Google Scholar
• Aoki T, Chong LC, Takata K, Milne K, Hav M, Colombo A, Chavez EA, Nissen M, Wang X, Miyata-Takata T, et al. Single-cell transcriptome analysis reveals disease-defining T-cell subsets in the tumor microenvironment of classic Hodgkin lymphoma. Cancer Discov. 2020;10(3):406–421. doi:10.1158/2159-8290.CD-19-0680.
   PubMed Web of Science ®Google Scholar
• Lambrechts D, Wauters E, Boeckx B, Aibar S, Nittner D, Burton O, Bassez A, Decaluwe H, Pircher A, Van Den Eynde K, et al. Phenotype molding of stromal cells in the lung tumor microenvironment. Nat Med. 2018;24(8):1277–1289. doi:10.1038/s41591-018-0096-5.
   PubMed Web of Science ®Google Scholar
• Kim N, Kim HK, Lee K, Hong Y, Cho JH, Choi JW, Lee JI, Suh YL, Ku BM, Eum HH, et al. Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. Nat Commun. 2020;11(1):2285. doi:10.1038/s41467-020-16164-1.
   PubMed Web of Science ®Google Scholar
• Azizi E, Carr AJ, Plitas G, Cornish AE, Konopacki C, Prabhakaran S, Nainys J, Wu K, Kiseliovas V, Setty M, et al. Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Cell. 2018;174(5):1293–1308e1236. doi:10.1016/j.cell.2018.05.060.
   PubMed Web of Science ®Google Scholar
• Cillo AR, Kurten CHL, Tabib T, Qi Z, Onkar S, Wang T, Liu A, Duvvuri U, Kim S, Soose RJ, et al. Immune landscape of viral- and carcinogen-driven head and neck cancer. Immunity. 2020;52(1):183–199e189. doi:10.1016/j.immuni.2019.11.014.
   PubMed Web of Science ®Google Scholar
• Zheng C, Zheng L, Yoo JK, Guo H, Zhang Y, Guo X, Kang B, Hu R, Huang JY, Zhang Q, et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell. 2017;169(7):1342–1356e1316. doi:10.1016/j.cell.2017.05.035.
   PubMed Web of Science ®Google Scholar
• Saelens W, Cannoodt R, Todorov H, Saeys Y. A comparison of single-cell trajectory inference methods. Nat Biotechnol. 2019;37(5):547–554. doi:10.1038/s41587-019-0071-9.
   PubMed Web of Science ®Google Scholar
• Chihara N, Madi A, Kondo T, Zhang H, Acharya N, Singer M, Nyman J, Marjanovic ND, Kowalczyk MS, Wang C, et al. Induction and transcriptional regulation of the co-inhibitory gene module in T cells. Nature. 2018;558(7710):454–459. doi:10.1038/s41586-018-0206-z.
   PubMed Web of Science ®Google Scholar
• Alfei F, Kanev K, Hofmann M, Wu M, Ghoneim HE, Roelli P, Utzschneider DT, Von Hoesslin M, Cullen JG, Fan Y, et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature. 2019;571(7764):265–269. doi:10.1038/s41586-019-1326-9.
   PubMed Web of Science ®Google Scholar
• Tosolini M, Algans C, Pont F, Ycart B, Fournie JJ. Large-scale microarray profiling reveals four stages of immune escape in non-Hodgkin lymphomas. Oncoimmunology. 2016;5(7):e1188246. doi:10.1080/2162402X.2016.1188246.
   PubMed Web of Science ®Google Scholar
• Kumar BV, Ma W, Miron M, Granot T, Guyer RS, Carpenter DJ, Senda T, Sun X, Ho S-H, Lerner H, et al. Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites. Cell Rep. 2017;20(12):2921–2934. doi:10.1016/j.celrep.2017.08.078.
   PubMed Web of Science ®Google Scholar