Journal
SCIENCE IMMUNOLOGY
Volume 2, Issue 11, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.aaj1738
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Funding
- NIH [R21NS090163]
- Brigham and Women's Hospital
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Regulatory T cells (T-regs ) promote cancer by suppressing antitumor immune responses. We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor-beta (TGF-beta) complex on T-regs and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases LAP T-regs , tolerogenic dendritic cells, and TGF-beta secretion and is associated with CD8(+) T cell activation. Anti-LAP increases infiltration of tumors by cytotoxic CD8(+) T cells and reduces CD103(+) CD8 T cells in draining lymph nodes and the spleen. We identified a role for CD103(+) CD8 T cells in cancer. Tumor-associated CD103(+) CD8 T cells have a tolerogenic phenotype with increased expression of CTLA-4 and interleukin-10 and decreased expression of interferon-gamma, tumor necrosis factor-alpha, and granzymes. Adoptive transfer of CD103(+) CD8 T cells promotes tumor growth, whereas CD103 blockade limits tumorigenesis. Thus, anti-LAP targets multiple immunoregulatory pathways and represents a potential approach for cancer immunotherapy.
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