Unknown

Dataset Information

0

Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy.


ABSTRACT: The biological and functional heterogeneity between tumors-both across and within cancer types-poses a challenge for immunotherapy. To understand the factors underlying tumor immune heterogeneity and immunotherapy sensitivity, we established a library of congenic tumor cell clones from an autochthonous mouse model of pancreatic adenocarcinoma. These clones generated tumors that recapitulated T cell-inflamed and non-T-cell-inflamed tumor microenvironments upon implantation in immunocompetent mice, with distinct patterns of infiltration by immune cell subsets. Co-injecting tumor cell clones revealed the non-T-cell-inflamed phenotype is dominant and that both quantitative and qualitative features of intratumoral CD8+ T cells determine response to therapy. Transcriptomic and epigenetic analyses revealed tumor-cell-intrinsic production of the chemokine CXCL1 as a determinant of the non-T-cell-inflamed microenvironment, and ablation of CXCL1 promoted T cell infiltration and sensitivity to a combination immunotherapy regimen. Thus, tumor cell-intrinsic factors shape the tumor immune microenvironment and influence the outcome of immunotherapy.

SUBMITTER: Li J 

PROVIDER: S-EPMC6707727 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


The biological and functional heterogeneity between tumors-both across and within cancer types-poses a challenge for immunotherapy. To understand the factors underlying tumor immune heterogeneity and immunotherapy sensitivity, we established a library of congenic tumor cell clones from an autochthonous mouse model of pancreatic adenocarcinoma. These clones generated tumors that recapitulated T cell-inflamed and non-T-cell-inflamed tumor microenvironments upon implantation in immunocompetent mice  ...[more]

Similar Datasets

| S-EPMC7057423 | biostudies-literature
| S-EPMC8683560 | biostudies-literature
| S-EPMC9732527 | biostudies-literature
| S-EPMC7311370 | biostudies-literature
| S-EPMC8639846 | biostudies-literature
| S-EPMC6986974 | biostudies-literature
| S-EPMC9216510 | biostudies-literature
| S-EPMC7409312 | biostudies-literature
| S-EPMC7225951 | biostudies-literature
| S-EPMC8177771 | biostudies-literature