Maximal T cell-mediated antitumor responses rely upon CCR5 expression in both CD4(+) and CD8(+) T cells

Area of Science:

• Immunology
• Oncology
• Cellular Biology

Background:

• Leukocyte trafficking, crucial for anti-cancer immunity, is regulated by chemokines.
• CCR5 (C-C chemokine receptor type 5) is a key receptor for chemokines like CCL3, CCL4, and CCL5, influencing T-cell mediated immunity.
• The precise role of CCR5 in tumor immune control remains under investigation.

Purpose of the Study:

• To investigate the specific, ligand-dependent role of CCR5 in optimizing anti-tumor immune responses.
• To determine the requirement of CCR5 expression on T cells for efficient tumor rejection.
• To elucidate the mechanisms by which CCR5 modulates T-cell activation and anti-tumor immunity.

Main Methods:

• Adoptive transfer studies using T cells with and without CCR5 expression.
• Analysis of CD40L upregulation, antigen-presenting cell maturation, and CD8(+) T-cell crosspriming and infiltration.
• Evaluation of CCR5's impact on chemically induced fibrosarcoma and spontaneous breast cancer progression in mice.
• Assessment of CCR5's role in TLR9-mediated anti-tumor responses.

Main Results:

• Efficient tumor rejection in adoptive transfer studies required CCR5 expression on both CD4(+) and CD8(+) T cells.
• CCR5 activation in CD4(+) T cells led to CD40L upregulation, enhancing antigen-presenting cell maturation and CD8(+) T-cell crosspriming and tumor infiltration.
• CCR5 reduced the incidence and growth of chemically induced fibrosarcomas.
• While not affecting spontaneous breast cancer onset, CCR5 was essential for TLR9-mediated reactivation of anti-tumor responses.

Conclusions:

• CCR5 plays a specific, ligand-dependent role in enhancing anti-tumor immune responses.
• CCR5 boosts T-cell responses to tumors by modulating helper-dependent CD8(+) T-cell activation.
• CCR5 is a critical mediator of adaptive anti-tumor immunity, influencing both T-cell priming and effector functions.