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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 12, 2019
- Source ID
- 10.1038/s41598-019-55368-4
Entities
People
- Grzegorz Sowa
- Guangfu Li
- Xiaoqiang Qi
- Yajun Liu
Organizations
- National Heart, Lung, and Blood Institute
- United States Department of Defense