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Coexpression of Inhibitory Receptors Enriches for Activated and Functional CD8 + T Cells in Murine Syngeneic Tumor Models.
- Source :
-
Cancer immunology research [Cancer Immunol Res] 2019 Jun; Vol. 7 (6), pp. 963-976. Date of Electronic Publication: 2019 May 07. - Publication Year :
- 2019
-
Abstract
- Exhausted T cells have been described in cancer patients and murine tumor models largely based on their expression of various inhibitory receptors. Understanding of the functional attributes of these cells is limited. Here, we report that among CD8 <superscript>+</superscript> T cells in commonly used syngeneic tumor models, the coexpression of inhibitory receptors PD-1, LAG3, and TIM3 defined a group of highly activated and functional effector cells. Coexpression of these receptors further enriched for antigen-specific cells with increased T-cell receptor clonality. Anti-PD-L1 treatment increased the number and activation of these triple-positive CD8 <superscript>+</superscript> T cells without affecting the density of PD-1 <superscript>-</superscript> cells. The intratumoral density of CD8 <superscript>+</superscript> T cells coexpressing inhibitory receptors negatively correlated with tumor burden. The density ratio and pretreatment phenotype of CD8 <superscript>+</superscript> T cells coexpressing inhibitory receptors was positively correlated with response across a variety of tumor models. Our results demonstrate that coexpression of inhibitory receptors is not a signifier of exhausted T cells, but rather can define a group of activated and functional effector cells in syngeneic tumor models. In the cancer setting, these cells could represent a heterogeneous population of not only exhausted but also highly activated cells responsive to treatment.<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Animals
B7-H1 Antigen antagonists & inhibitors
Biomarkers, Tumor
Cell Line, Tumor
Cytotoxicity, Immunologic
Disease Models, Animal
Epitopes, T-Lymphocyte immunology
Female
Hepatocyte Nuclear Factor 1-alpha genetics
Hepatocyte Nuclear Factor 1-alpha metabolism
Isografts
Mice
Neoplasms pathology
T-Box Domain Proteins genetics
T-Box Domain Proteins metabolism
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes metabolism
Costimulatory and Inhibitory T-Cell Receptors genetics
Lymphocyte Activation genetics
Lymphocyte Activation immunology
Neoplasms etiology
Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2326-6074
- Volume :
- 7
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cancer immunology research
- Publication Type :
- Academic Journal
- Accession number :
- 31064777
- Full Text :
- https://doi.org/10.1158/2326-6066.CIR-18-0750