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Caveolin-2 deficiency induces a rapid anti-tumor immune response prior to regression of implanted murine lung carcinoma tumors.


ABSTRACT: Immunosuppression is critical for tumor growth and metastasis as well as obstacle to effective immunotherapy. Here, we demonstrate that host deficiency in caveolin-2, a member of caveolin protein family, increases M1-polarized tumor-associated macrophage (TAM) and CD8 T cell infiltration into subcutaneously implanted murine lung carcinoma tumors. Importantly, increase in M1 TAM-specific markers and cytokines occurs prior to increased numbers of tumor-infiltrating CD8 T cells and tumor regression in caveolin-2 deficient mice, suggesting that an early increase in M1 TAMs is a novel mechanism, via which host deficiency in caveolin-2 inhibits tumor growth. Consistent with the latter, transfer and co-injection of caveolin-2 deficient bone marrow (origin of TAMs) suppresses tumor growth and increases numbers of M1-polarized TAMs in wild type mice. Collectively, our data suggest that lung cancer cells use caveolin-2 expressed in bone marrow-derived cell types including TAMs to promote tumor growth via suppressing the anti-tumor immune response and that caveolin-2 could be a potential target for cancer immunotherapy.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC6908574 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Caveolin-2 deficiency induces a rapid anti-tumor immune response prior to regression of implanted murine lung carcinoma tumors.

Liu Yajun Y   Qi Xiaoqiang X   Li Guangfu G   Sowa Grzegorz G  

Scientific reports 20191212 1


Immunosuppression is critical for tumor growth and metastasis as well as obstacle to effective immunotherapy. Here, we demonstrate that host deficiency in caveolin-2, a member of caveolin protein family, increases M1-polarized tumor-associated macrophage (TAM) and CD8 T cell infiltration into subcutaneously implanted murine lung carcinoma tumors. Importantly, increase in M1 TAM-specific markers and cytokines occurs prior to increased numbers of tumor-infiltrating CD8 T cells and tumor regression  ...[more]

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