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.
Highlights
Immunosuppression is critical for tumor growth and metastasis as well as obstacle to effective immunotherapy
Using a subcutaneously inoculated Lewis lung carcinoma (LLC) model of lung tumor growth in mice, we show a rapid increase in infiltration of M1-polarized and activated tumor-associated macrophage (TAM) followed by CD4 and CD8 T cell infiltration and regression of tumors implanted into Cav-2 knockout (KO) mice
Our data suggest that lung cancer cells use Cav-2 expressed in bone marrow-derived cell types including TAMs to promote tumor growth via inhibiting the anti-tumor immune response and that Cav-2 could be a potential target for cancer immunotherapy
Summary
Immunosuppression is critical for tumor growth and metastasis as well as obstacle to effective immunotherapy. 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. We demonstrate for the first time that caveolin-2 (Cav-2), a member of caveolin protein family that is largely dissimilar from its better known cousin, caveolin-1 in their amino acid sequence and function[21,22,23,24,25], is critical for lung cancer growth through novel mechanisms involving TAMs and suppression of the anti-tumor immune response. Our data suggest that lung cancer cells use Cav-2 expressed in bone marrow-derived cell types including TAMs to promote tumor growth via inhibiting the anti-tumor immune response and that Cav-2 could be a potential target for cancer immunotherapy
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