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Cited by 68Cancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesImmune cells in cancer

TIGIT/CD155 blockade enhances anti-PD-L1 therapy in head and neck squamous cell carcinoma by targeting myeloid-derived suppressor cells

Mao, Liang, Xiao, Yao, Yang, Qi-Chao, Yang, Shao-Chen, Yang, Lei-Lei, Sun, Zhi-Jun·2021·Oral Oncology
DOI 10.1016/j.oraloncology.2021.105472
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Abstract

Objectives Anti-PD-1/PD-L1 therapy has recently been approved for head and neck squamous cell carcinoma (HNSCC). However, given that large numbers of patients with HNSCC do not respond to PD-1/PD-L1 antibodies, combination strategies for elevating the response rate need to be further investigated. The goal of this study was to explore the possibility of dual-targeting CD155/TIGIT and PD-1/PD-L1 signalling in HNSCC.Materials and methods Multiplex flow cytometry was performed to determine the co-expression of CD155 and PD-L1 in human HNSCC and transgenic HNSCC mouse models. The combined application of TIGIT mAb and PD-L1 mAb in a mouse model was used to explore the therapeutic effect.Results CD155 and PD-L1 were highly co-expressed on myeloid-derived suppressor cells (MDSCs) derived from patients with HNSCC and were inversely associated with the percentage of tumour CD3+ T and effector memory T cells. CD155+PD-L1+ MDSCs in the mouse model were gradually enriched in the tumour microenvironment in the middle and late stages of tumour progression. Anti-PD-L1 treatment alone upregulated the expression of CD155 on MDSCs and while anti-TIGIT treatment upregulated the expression of PD-L1 on MDSCs in mice. The combined blockade of TIGIT/CD155 and PD-1/PD-L1 signalling in mice significantly inhibited tumour growth, enhanced the percentages of effector T cells and cytokine secretion and elicited immune memory effects.Conclusion Our study indicated that CD155+PD-L1+ MDSCs are enriched in the tumour microenvironment and blocking TIGIT/CD155 can effectively enhance the response rate of HNSCC to PD-L1 mAb therapy, which provides the clinical potential of co-targeting TIGIT/CD155 and PD-1/PD-L1 signalling.

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Crossref · 10.1016/j.oraloncology.2021.105472

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  • Other ICIs such as α-LAG-3, α-PVRIG, α-TIGIT, α-Siglec-10 also synergized with α-PD-1/PD-L1 in enhancing TIL function and suppressing tumor growth.

    “Besides α-TIM-3, other ICIs such as α-LAG-3, α-PVRIG, α-TIGIT, α- Siglec-10 also synergized with α-PD-1/PD-L1 in enhancing TIL function and suppressing tumor growth [161–164].”

    From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [163]

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Authors
Mao, L., Xiao, Y., Yang, Q.-C., Yang, S.-C., Yang, L.-L., & Sun, Z.-J.
Affiliations
Wuhan University (CN)
Corresponding author
Sun, Zhi-Jun
ORCID
Venue
Oral Oncology
Publisher
Elsevier BV
Published
2021-10
Volume
121
Pages
105472
ISSN
1368-8375 (ISSN-L)
DOI
10.1016/j.oraloncology.2021.105472
OpenAlex
W3190318989
Cited by
68
References
39
Citations by year
2026: 7 · 2025: 22 · 2024: 8 · 2023: 15 · 2022: 14 · 2021: 2
FWCI
3.57
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oral Oncology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
TIGIT, CD155, PD-L1, PD-1, head and neck squamous cell carcinoma, myeloid-derived suppressor cells, immune checkpoint blockade, combination immunotherapy, tumor microenvironment, effector T cells, immunological memory, PD-L1 inhibitors
MeSH terms
Myeloid-Derived Suppressor Cells, Squamous Cell Carcinoma of Head and Neck, Memory T Cells, Animals, Antibodies, Monoclonal, Head and Neck Neoplasms, Humans, Receptors, Immunologic, Receptors, Virus, Mice, Tumor Microenvironment, B7-H1 Antigen

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