PMID- 32699351
OWN - NLM
STAT- MEDLINE
DCOM- 20211006
LR  - 20230919
IS  - 2042-0226 (Electronic)
IS  - 1672-7681 (Print)
IS  - 1672-7681 (Linking)
VI  - 17
IP  - 9
DP  - 2020 Sep
TI  - Cancer immunotherapy with gammadelta T cells: many paths ahead of us.
PG  - 925-939
LID - 10.1038/s41423-020-0504-x [doi]
AB  - gammadelta T cells play uniquely important roles in stress surveillance and immunity for 
      infections and carcinogenesis. Human gammadelta T cells recognize and kill transformed 
      cells independently of human leukocyte antigen (HLA) restriction, which is an 
      essential feature of conventional alphabeta T cells. Vgamma9Vdelta2 gammadelta T cells, which prevail in 
      the peripheral blood of healthy adults, are activated by microbial or endogenous 
      tumor-derived pyrophosphates by a mechanism dependent on butyrophilin molecules. 
      gammadelta T cells expressing other T cell receptor variable genes, notably Vdelta1, are more 
      abundant in mucosal tissue. In addition to the T cell receptor, gammadelta T cells 
      usually express activating natural killer (NK) receptors, such as NKp30, NKp44, 
      or NKG2D which binds to stress-inducible surface molecules that are absent on 
      healthy cells but are frequently expressed on malignant cells. Therefore, gammadelta T 
      cells are endowed with at least two independent recognition systems to sense 
      tumor cells and to initiate anticancer effector mechanisms, including cytokine 
      production and cytotoxicity. In view of their HLA-independent potent antitumor 
      activity, there has been increasing interest in translating the unique potential 
      of gammadelta T cells into innovative cellular cancer immunotherapies. Here, we discuss 
      recent developments to enhance the efficacy of gammadelta T cell-based immunotherapy. 
      This includes strategies for in vivo activation and tumor-targeting of gammadelta T 
      cells, the optimization of in vitro expansion protocols, and the development of 
      gene-modified gammadelta T cells. It is equally important to consider potential 
      synergisms with other therapeutic strategies, notably checkpoint inhibitors, 
      chemotherapy, or the (local) activation of innate immunity.
FAU - Kabelitz, Dieter
AU  - Kabelitz D
AUID- ORCID: 0000-0002-4160-7103
AD  - Institute of Immunology, Christian-Albrechts University of Kiel and University 
      Hospital Schleswig-Holstein Campus Kiel, D-24105, Kiel, Germany. 
      dietrich.kabelitz@uksh.de.
FAU - Serrano, Ruben
AU  - Serrano R
AD  - Institute of Immunology, Christian-Albrechts University of Kiel and University 
      Hospital Schleswig-Holstein Campus Kiel, D-24105, Kiel, Germany.
FAU - Kouakanou, Leonce
AU  - Kouakanou L
AD  - Institute of Immunology, Christian-Albrechts University of Kiel and University 
      Hospital Schleswig-Holstein Campus Kiel, D-24105, Kiel, Germany.
FAU - Peters, Christian
AU  - Peters C
AUID- ORCID: 0000-0002-7669-3806
AD  - Institute of Immunology, Christian-Albrechts University of Kiel and University 
      Hospital Schleswig-Holstein Campus Kiel, D-24105, Kiel, Germany.
FAU - Kalyan, Shirin
AU  - Kalyan S
AUID- ORCID: 0000-0002-7332-2225
AD  - Faculty of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z4, 
      Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20200722
PL  - China
TA  - Cell Mol Immunol
JT  - Cellular & molecular immunology
JID - 101242872
RN  - 0 (Ligands)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
SB  - IM
EIN - Cell Mol Immunol. 2020 Sep 1;:. PMID: 32873864
MH  - Animals
MH  - Humans
MH  - *Immunotherapy
MH  - Ligands
MH  - Lymphocyte Activation/immunology
MH  - Lymphocytes, Tumor-Infiltrating/immunology
MH  - Neoplasms/*immunology/*therapy
MH  - Receptors, Antigen, T-Cell, gamma-delta/*metabolism
PMC - PMC7609273
OTO - NOTNLM
OT  - Adoptive T cell transfer
OT  - Antibody constructs
OT  - Cytokines
OT  - Immunotherapy
OT  - Leukemia
OT  - Lymphoma
OT  - Solid tumors
OT  - gamma/delta T cells
COIS- D.K. is a member of the Scientific Advisory Board of Incysus Therapeutics, Inc.; 
      Imcheck Therapeutics; Lava Therapeutics B.V.; and Qu Biologics, Inc. S.K. is the 
      Scientific Director of Qu Biologics, Inc. The remaining authors declare no 
      competing interests.
EDAT- 2020/07/24 06:00
MHDA- 2021/10/07 06:00
PMCR- 2020/07/22
CRDT- 2020/07/24 06:00
PHST- 2020/05/22 00:00 [received]
PHST- 2020/06/27 00:00 [accepted]
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2021/10/07 06:00 [medline]
PHST- 2020/07/24 06:00 [entrez]
PHST- 2020/07/22 00:00 [pmc-release]
AID - 10.1038/s41423-020-0504-x [pii]
AID - 504 [pii]
AID - 10.1038/s41423-020-0504-x [doi]
PST - ppublish
SO  - Cell Mol Immunol. 2020 Sep;17(9):925-939. doi: 10.1038/s41423-020-0504-x. Epub 
      2020 Jul 22.