Impact of tumor-derived CCL2 on T cell effector function.
To study the effects of tumor-derived monocyte chemoattractant protein-1 (MCP-1, CCL2) on the anti-tumor immune response we used the 4T1 murine mammary carcinoma which constitutively expresses CCL2. We generated 4T1 that do not express detectable levels of CCL2 and found that the T cell response to the tumors were altered. Lymph nodes draining the CCL2- tumor contained CD62Llo cells that produced greater levels of INF-gamma in response to the tumor than CD62Llo cells from lymph nodes draining a tumor that produced CCL2. Moreover, exposure of splenic T cells to recombinant CCL2 in vitro decreased the ability of the T cells to produce IFN-gamma. However, despite the enhanced effector function evident in the absence of CCL2, vaccination/challenge experiments failed to reveal an increase in immunogenicity of the CCL2 null cells relative to the CCL2+ cells. Collectively, these data indicate that tumor-derived CCL2 could decrease T cell effector function, yet not the overall immunogenicity of the tumor.
Vitiello
Peter F
PF
Department of Biology, Lafayette College, Easton, PA 18042, USA.
Shainheit
Mara G
MG
Allison
Erin M
EM
Adler
Evan P
EP
Kurt
Robert A
RA
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D007371:Interferon-gamma / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D019041:L-Selectin; D007371:Interferon-gamma