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PGRN inhibits CD8+T cell recruitment and promotes breast cancer progression by up-regulating ICAM-1 on TAM.
- Source :
- Cancer Immunology, Immunotherapy; May2024, Vol. 73 Issue 5, p1-19, 19p
- Publication Year :
- 2024
-
Abstract
- Background: Tumor microenvironment actually reduces antitumor effect against the immune attack by exclusion of CD8<superscript>+</superscript>T cells. Progranulin (PGRN) is a multifunctional growth factor with significant pathological effects in multiple tumors; however, its role in immunity evasion of breast cancer (BCa) is not completely understood. Methods: We depleted GRN (PGRN gene) genetically in mice or specifically in PY8119 murine BCa cell line, and mouse models of orthotopic or subcutaneous transplantation were used. Chimeric mice-deficient of PGRN (Grn<superscript>−/−</superscript>) in bone marrow (BM) compartment was also generated. Association of PGRN expression with chemokine production or BCa development was investigated by histological and immunological assays. Results: We found PGRN was involved in exhaustion of cytotoxic CD8<superscript>+</superscript>T cell in BCa with the increasing expressions of M2 markers and intercellular cell adhesion molecule-1 (ICAM-1) on macrophages. Specifically, ablation of PGRN in PY8119 cells reduced tumor burden, accompanied by the infiltrating of cytotoxic CD8<superscript>+</superscript>T cells into tumor nests. Moreover, our result revealed that blockade of PD-1 in PGRN-depleted tumors exhibited better antitumor effect in vivo and significantly decreased tumor burden. Conclusion: These findings suggest that inhibition of PGRN may act as a potential immune-therapeutic strategy by recovering infiltration of CD8<superscript>+</superscript>T cell in BCa tissue and thereby enhancing the response to anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03407004
- Volume :
- 73
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Cancer Immunology, Immunotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 176340127
- Full Text :
- https://doi.org/10.1007/s00262-024-03655-z