Exploration of Immunology

Table 1. Main features of γδ T cells in humans and mice with pro- or anti-tumor activity.

γδ T cell population	Species	Model study	Main features	Molecules on lymphocytes	Molecules/Factors on epithelial cells	Ref.
Vγ5	Mouse	Healthy colon β7^–/– mice mAb to α4β7 or MAdCAM-1 RALDH deficiency	Impaired localization	CCR9, αEβ7	CCL25, E-cadherin	[24, 25]
γδ T cells Vγ7⁺	Mouse	Healthy colon, AhR deficient alleles	Impaired localization	Granzymes, C-type lectins, GPR18, GPR55	IL-7, IL-15, MMP-7	[43–45]
non-Vδ1-Vδ2 Vγ7 Vγ6	Mouse/Human		Suppressor antitumor cells	CD8α⁺ PD-1⁻		[54, 73]
Vδ1Vγ2⁺ Vδ1	Human	CRC, FC, IHC	IL-17 producer, MDSC recruitment		ARG1–2, IDO	[48, 50, 52–55]
Vδ1 in breast and prostate cancers	Human	FC, regulatory activity in vitro and in vivo NOD SCID mice	Suppressor cells IKKα, IKKβ mediated	TLR11, TLR7, TLR8, MyD88	TLR8L Poly-G3 ssRNA40 Reversed suppression	[71]
Vδ1	Human	CRC, healthy mucosa, FC, TCR seq, IHC, functional in vitro experiments	Potent cytotoxic cells IFN-γ	NKp46⁺ NKp44⁺ NKp30⁺ NKG2C⁺ NKG2D CD8α⁺ CD56 CD16^low	Ligands for activatory receptors IL-2 IL-15	[78]
non-Vδ1-Vδ2 Vδ1, Vδ4 Vδ5, Vδ7 Vδ8	Human	Humanized CRC, MS, FC, TCR seq	TGF-β, Galectin 3, AREG	Low production of IFN-γ	No correlation with stage, MSS or MSI	[51, 72]

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AhR: aryl hydrocarbon receptor; αEβ7: integrin αE integrin β7; ARG1–2: arginase 1, 2; CCL25: chemokine (C-C motif) ligand 25; CCR9: CC chemokine receptor type 9; FC: flow cytometry; GPR18: G-protein coupled receptor 18; GPR55: G-protein coupled receptor 55; IDO: indoleamine 2,3-dioxygenase; IHC: immunohistochemistry; IKKα: inhibitor of nuclear factor-κB (IκB) kinase α; IKKβ: inhibitor of nuclear factor-κB (IκB) kinase β; MAdCAM: mucosal addressin cell adhesion molecule; MDSC: myeloid derived suppressor cells; MMP-7: matrix metalloproteinase 7; MS: mass spectrometry; MSI: microsatellite instability; MSS: microsatellite stability; Poly-G3: a guanosine-rich, phosphorothioate-modified oligodeoxynucleotide; NOD-SCID: non obese diabetic severe combined immunodeficiency; RALDH: retinal dehydrogenase; ssRNA40: GU-rich single-stranded RNA; TCR-seq: T cell receptor sequencing; TGF: transforming growth factor; TLR8L: toll-like receptor 8 ligand.

Declarations

Acknowledgments

All the figures have been designed from the templates of Anatomy and Human Body and Cellular Biology series of Smart Servier Medical Art (https://smart.servier.com/).

Author contributions

AP: Conceptualization, Investigation, Validation, Supervision, Writing—original draft, Writing—review & editing. The author read and approved the submitted version.

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The author declares that he has no conflicts of interest.

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The manuscript has been supported by the grant AIRCIG21648 to AP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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