Targeting latency-associated peptide promotes antitumor immunity

Galina Gabriely, Andre P. Da Cunha, Rafael M. Rezende, Brendan Kenyon, Asaf Madi, Tyler Vandeventer, Nathaniel Skillin, Stephen Rubino, Lucien Garo, Maria A. Mazzola, Panagiota Kolypetri, Amanda J. Lanser, Thais Moreira, Ana Maria C. Faria, Hans Lassmann, Vijay Kuchroo, Gopal Murugaiyan, Howard L. Weiner

Research output: Contribution to journalArticlepeer-review


Regulatory T cells (Tregs) promote cancer by suppressing antitumor immune responses. We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor– (TGF-) complex on Tregs and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases LAP+ Tregs, tolerogenic dendritic cells, and TGF- 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-, tumor necrosis factor–, 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.

Original languageEnglish
Article numbereaaj1738
JournalScience immunology
Issue number11
StatePublished - 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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