Targeting Latency-associated Peptide Promotes Antitumor Immunity

Overview

Journal Sci Immunol

Specialty Allergy & Immunology

Date 2017 Aug 2

PMID 28763794

Citations 45

Authors

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

Affiliations

Soon will be listed here.

Abstract

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