Vγ9Vδ2 T-cell immunotherapy in blood cancers: ready for prime time?

Front Immunol. 2023 Apr 18:14:1167443. doi: 10.3389/fimmu.2023.1167443. eCollection 2023.

Abstract

In the last years, the tumor microenvironment (TME) has emerged as a promising target for therapeutic interventions in cancer. Cancer cells are highly dependent on the TME to growth and evade the immune system. Three major cell subpopulations are facing each other in the TME: cancer cells, immune suppressor cells, and immune effector cells. These interactions are influenced by the tumor stroma which is composed of extracellular matrix, bystander cells, cytokines, and soluble factors. The TME can be very different depending on the tissue where cancer arises as in solid tumors vs blood cancers. Several studies have shown correlations between the clinical outcome and specific patterns of TME immune cell infiltration. In the recent years, a growing body of evidence suggests that unconventional T cells like natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells, and γδ T cells are key players in the protumor or antitumor TME commitment in solid tumors and blood cancers. In this review, we will focus on γδ T cells, especially Vγ9Vδ2 T cells, to discuss their peculiarities, pros, and cons as potential targets of therapeutic interventions in blood cancers.

Keywords: Vγ9Vδ2 T cells; adoptive cell transfer; blood cancers; immunotherapy; unconventional T cells.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / pathology
  • Hematologic Neoplasms*
  • Humans
  • Immunotherapy
  • Neoplasms*
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Microenvironment

Substances

  • Receptors, Antigen, T-Cell, gamma-delta

Grants and funding

This study received funding from the Italian Association for Cancer Research (AIRC) (IG21744 to MM), Associazione Italiana contro le Leucemie-Linfomi e Mielomi ONLUS (AIL) (Sezione Paolo Rubino di Cuneo) (MM, FA), and Sanofi (Research-to-Care OncoHematology). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.