Abstract
Effector T cells have the capability of recognizing and killing cancer cells. However, whether tumors can become immune resistant through exclusion of effector T cells from the tumor microenvironment is not known. By using a tumor model resembling non-T cell-inflamed human tumors, we assessed whether adoptive T cell transfer might overcome failed spontaneous priming. Flow cytometric assays combined with intra-vital imaging indicated failed trafficking of effector T cells into tumors. Mechanistically, this was due to the absence of CXCL9/10, which we found to be produced by CD103+ dendritic cells (DCs) in T cell-inflamed tumors. Our data indicate that lack of CD103+ DCs within the tumor microenvironment dominantly resists the effector phase of an anti-tumor T cell response, contributing to immune escape.
Keywords:
T cell-inflamed tumor microenvironment; adoptive T cell transfer; immune escape; immunotherapy resistance; non-T cell-inflamed tumor microenvironment.
Copyright © 2017 Elsevier Inc. All rights reserved.
MeSH terms
-
Animals
-
Antigens, CD / metabolism
-
Basic-Leucine Zipper Transcription Factors / deficiency
-
Basic-Leucine Zipper Transcription Factors / genetics
-
Basic-Leucine Zipper Transcription Factors / metabolism*
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / metabolism
-
Cell Line, Tumor
-
Cell Proliferation
-
Chemokine CXCL10 / metabolism
-
Chemokine CXCL9 / metabolism
-
Chemotaxis, Leukocyte*
-
Dendritic Cells / immunology
-
Dendritic Cells / metabolism*
-
Genotype
-
Immunologic Memory
-
Immunotherapy, Adoptive / methods*
-
Integrin alpha Chains / metabolism
-
Melanoma / immunology
-
Melanoma / metabolism
-
Melanoma / pathology
-
Melanoma / therapy*
-
Mice, Knockout
-
Phenotype
-
Repressor Proteins / deficiency
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism*
-
Signal Transduction
-
Skin Neoplasms / immunology
-
Skin Neoplasms / metabolism
-
Skin Neoplasms / pathology
-
Skin Neoplasms / therapy*
-
T-Lymphocytes / immunology
-
T-Lymphocytes / metabolism
-
T-Lymphocytes / transplantation*
-
Time Factors
-
Tumor Burden
-
Tumor Escape*
-
Tumor Microenvironment
-
beta Catenin / metabolism
Substances
-
Antigens, CD
-
BATF3 protein, human
-
Basic-Leucine Zipper Transcription Factors
-
CTNNB1 protein, mouse
-
Chemokine CXCL10
-
Chemokine CXCL9
-
Cxcl10 protein, mouse
-
Cxcl9 protein, mouse
-
Integrin alpha Chains
-
Repressor Proteins
-
SNFT protein, mouse
-
alpha E integrins
-
beta Catenin