Details

Autor(en) / Beteiligte

• Reis, Bernardo S
• Darcy, Patrick W
• Khan, Iasha Z
• Moon, Christine S
• Kornberg, Adam E
• Schneider, Vanessa S
• Alvarez, Yelina
• Eleso, Olawale
• Zhu, Caixia
• Schernthanner, Marina
• Lockhart, Ainsley
• Reed, Aubrey
• Bortolatto, Juliana
• Castro, Tiago B R
• Bilate, Angelina M
• Grivennikov, Sergei
• Han, Arnold S
• Mucida, Daniel

Titel

TCR-Vγδ usage distinguishes protumor from antitumor intestinal γδ T cell subsets

Ist Teil von

• Science (American Association for the Advancement of Science), 2022-07, Vol.377 (6603), p.276-284

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• γδ T cells represent a substantial fraction of intestinal lymphocytes at homeostasis, but they also constitute a major lymphocyte population infiltrating colorectal cancers (CRCs); however, their temporal contribution to CRC development or progression remains unclear. Using human CRC samples and murine CRC models, we found that most γδ T cells in premalignant or nontumor colons exhibit cytotoxic markers, whereas tumor-infiltrating γδ T cells express a protumorigenic profile. These contrasting T cell profiles were associated with distinct T cell receptor (TCR)-Vγδ gene usage in both humans and mice. Longitudinal intersectional genetics and antibody-dependent strategies targeting murine γδ T cells enriched in the epithelium at steady state led to heightened tumor development, whereas targeting γδ subsets that accumulate during CRC resulted in reduced tumor growth. Our results uncover temporal pro- and antitumor roles for γδ T cell subsets.