Exploration of Immunology

Table 4. Features of CRC cells and TME to select patient immunotherapy with γδ T cells and possible combos with drugs or immune cells.

CRC subtypes, main features	γδ T cell infiltration (degree and features)	Targeting molecules for γδ T cell activation on CRC cells	Combinations of drugs/cells with γδ T cells
CMS1: MSI immune MSI, SCNA^low, BRAFm, TIL	Good	EGFR BTN and BTN-like, NKG2DL, DNAM-1L functional APC	Anti-EGFR-mAb linked to N-BPs or pAgs
CMS2: canonical WNT, MYC, SCNA^high	Medium/Low	EGFR BTN and BTN-like, NKG2DL, DNAM-1L functional APC	Anti-EGFR mAb
CMS3: metabolic SCNA^low, KRAS	Low/Impaired by TME	EGFR BTN and BTN-like, NKG2DL, DNAM-1L functional APC	Anti-EGFR mAb, metformin, HIF1α inhibitors
CMS4: mesenchymal TGF-β, stromal, EMT, SCNA^high	Low/Strongly impaired by TME	EGFR BTN and BTN-like, NKG2DL, DNAM-1L functional APC	Anti-VEGF mAb, anti-TGF mAb, anti-MSC mAb, anti-LAIR-1 mAb

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BRAFm: mutation gene for serine/threonine-protein kinase B-Raf; CMS: consensus molecular subtype; N-BPs: aminobisphosphonates; MSI: microsatellite instability; SCNA: somatic copy number alteration; EMT: epithelial-mesenchymal transition; TGF: transforming growth factor; TIL: tumor infiltrating lymphocyte.

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.

Conflicts of interest

The author declares that he has no conflicts of interest.

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Funding

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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