Targeting latency-associated peptide promotes antitumor immunity

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.