MHC Class Ib-restricted CD8 T Cells Possess Strong Tumoricidal Activities

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2023 Oct 19

PMID 37856544

Authors

Qing Li

Liangyu Lin

Peishun Shou

Keli Liu

Yueqing Xue

Mingyuan Hu

Weifang Ling

Yin Huang

Liming Du

Chunxing Zheng

Xuefeng Wang

Fanjun Zheng

Tao Zhang

Yu Wang

Changshun Shao

Gerry Melino

Yufang Shi

Ying Wang

Affiliations

Soon will be listed here.

Abstract

The importance of classical CD8 T cells in tumor eradication is well acknowledged. However, the anti-tumor activity of MHC (major histocompatibility complex) Ib-restricted CD8 T (Ib-CD8 T) cells remains obscure. Here, we show that CX3CR1-expressing Ib-CD8 T cells (Ib-restricted CD8 T cells) highly express cytotoxic factors, austerely resist exhaustion, and effectively eliminate various tumors. These Ib-CD8 T cells can be primed by MHC Ia (MHC class Ia molecules) expressed on various cell types for optimal activation in a Tbet-dependent manner. Importantly, MHC Ia does not allogeneically activate Ib-CD8 T cells, rather, sensitizes these cells for T cell receptor activation. Such effects were observed when MHC Ia cells were administered to tumor-bearing KDmice. A similar population of tumoricidal CX3CR1CD8 T cells was identified in wild-type mice and melanoma patients. Adoptive transfer of Ib-CD8 T cells to wild-type mice inhibited tumor progression without damaging normal tissues. Taken together, we demonstrate that MHC class Ia can prime Ib-CD8 T cells for robust tumoricidal activities.

Citing Articles

MHC class Ib-restricted CD8 T cells possess strong tumoricidal activities.

Li Q, Lin L, Shou P, Liu K, Xue Y, Hu M Proc Natl Acad Sci U S A. 2023; 120(43):e2304689120.

PMID: 37856544 PMC: 10614629. DOI: 10.1073/pnas.2304689120.

References

Ahrends T, Spanjaard A, Pilzecker B, Babala N, Bovens A, Xiao Y . CD4 T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness. Immunity. 2017; 47(5):848-861.e5. DOI: 10.1016/j.immuni.2017.10.009. View

Francois M, Romieu-Mourez R, Stock-Martineau S, Boivin M, Bramson J, Galipeau J . Mesenchymal stromal cells cross-present soluble exogenous antigens as part of their antigen-presenting cell properties. Blood. 2009; 114(13):2632-8. DOI: 10.1182/blood-2009-02-207795. View

Hansen S, Wu H, Burwitz B, Hughes C, Hammond K, Ventura A . Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E. Science. 2016; 351(6274):714-20. PMC: 4769032. DOI: 10.1126/science.aac9475. View

Ogasawara K, Hamerman J, Ehrlich L, Bour-Jordan H, Santamaria P, Bluestone J . NKG2D blockade prevents autoimmune diabetes in NOD mice. Immunity. 2004; 20(6):757-67. DOI: 10.1016/j.immuni.2004.05.008. View

Ren G, Zhao X, Wang Y, Zhang X, Chen X, Xu C . CCR2-dependent recruitment of macrophages by tumor-educated mesenchymal stromal cells promotes tumor development and is mimicked by TNFα. Cell Stem Cell. 2012; 11(6):812-24. PMC: 3518598. DOI: 10.1016/j.stem.2012.08.013. View

Chiang E, Henson M, Stroynowski I . Correction of defects responsible for impaired Qa-2 class Ib MHC expression on melanoma cells protects mice from tumor growth. J Immunol. 2003; 170(9):4515-23. DOI: 10.4049/jimmunol.170.9.4515. View

Godfrey D, Uldrich A, McCluskey J, Rossjohn J, Moody D . The burgeoning family of unconventional T cells. Nat Immunol. 2015; 16(11):1114-23. DOI: 10.1038/ni.3298. View

Yamauchi T, Hoki T, Oba T, Saito H, Attwood K, Sabel M . CX3CR1-CD8+ T cells are critical in antitumor efficacy but functionally suppressed in the tumor microenvironment. JCI Insight. 2020; 5(8). PMC: 7205436. DOI: 10.1172/jci.insight.133920. View

Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts A . Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008; 2(2):141-50. DOI: 10.1016/j.stem.2007.11.014. View

10.

Chen L, Jay D, Fairbanks J, He X, Jensen P . An MHC class Ib-restricted CD8+ T cell response to lymphocytic choriomeningitis virus. J Immunol. 2011; 187(12):6463-72. PMC: 4042437. DOI: 10.4049/jimmunol.1101171. View

11.

Das G, Das J, Eynott P, Zhang Y, Bothwell A, Van Kaer L . Pivotal roles of CD8+ T cells restricted by MHC class I-like molecules in autoimmune diseases. J Exp Med. 2006; 203(12):2603-11. PMC: 2118151. DOI: 10.1084/jem.20060936. View

12.

Nabekura T, Gotthardt D, Niizuma K, Trsan T, Jenus T, Jonjic S . Cutting Edge: NKG2D Signaling Enhances NK Cell Responses but Alone Is Insufficient To Drive Expansion during Mouse Cytomegalovirus Infection. J Immunol. 2017; 199(5):1567-1571. PMC: 5567695. DOI: 10.4049/jimmunol.1700799. View

13.

Anderson C, Brossay L . The role of MHC class Ib-restricted T cells during infection. Immunogenetics. 2016; 68(8):677-91. PMC: 5003733. DOI: 10.1007/s00251-016-0932-z. View

14.

Radwan J, Babik W, Kaufman J, Lenz T, Winternitz J . Advances in the Evolutionary Understanding of MHC Polymorphism. Trends Genet. 2020; 36(4):298-311. DOI: 10.1016/j.tig.2020.01.008. View

15.

Bosc N, Lefranc M . The mouse (Mus musculus) T cell receptor beta variable (TRBV), diversity (TRBD) and joining (TRBJ) genes. Exp Clin Immunogenet. 2000; 17(4):216-28. DOI: 10.1159/000019141. View

16.

Vugmeyster Y, Glas R, Perarnau B, Lemonnier F, Eisen H, Ploegh H . Major histocompatibility complex (MHC) class I KbDb -/- deficient mice possess functional CD8+ T cells and natural killer cells. Proc Natl Acad Sci U S A. 1998; 95(21):12492-7. PMC: 22858. DOI: 10.1073/pnas.95.21.12492. View

17.

Forman J, Lindahl K . Listing, location, binding motifs, and expression of nonclassical class I and related genes and molecules. Curr Protoc Immunol. 2008; Appendix 1:Appendix 1M. DOI: 10.1002/0471142735.ima01ms49. View

18.

Hudson W, Gensheimer J, Hashimoto M, Wieland A, Valanparambil R, Li P . Proliferating Transitory T Cells with an Effector-like Transcriptional Signature Emerge from PD-1 Stem-like CD8 T Cells during Chronic Infection. Immunity. 2019; 51(6):1043-1058.e4. PMC: 6920571. DOI: 10.1016/j.immuni.2019.11.002. View

19.

Azizi E, Carr A, Plitas G, Cornish A, Konopacki C, Prabhakaran S . Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. Cell. 2018; 174(5):1293-1308.e36. PMC: 6348010. DOI: 10.1016/j.cell.2018.05.060. View

20.

Jerby-Arnon L, Shah P, Cuoco M, Rodman C, Su M, Melms J . A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade. Cell. 2018; 175(4):984-997.e24. PMC: 6410377. DOI: 10.1016/j.cell.2018.09.006. View