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Cited by 54Cancer Immunotherapy and BiomarkersNonmelanoma Skin Cancer StudiesPhotodynamic Therapy Research Studies

PD-L1 blockade potentiates the antitumor effects of ALA-PDT and optimizes the tumor microenvironment in cutaneous squamous cell carcinoma

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Zeng, Qingyu, Yang, Jiayi, Ji, Jie, Wang, Peiru, Zhang, Linglin, Yan, Guorong, Wu, Yuhao, Chen, Qi +3 more·2022·OncoImmunology
DOI 10.1080/2162402x.2022.2061396PMC PMC8986186
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Abstract

Immune checkpoint blockade (ICB) is a powerful oncologic treatment modality for a wide variety of human malignancies, but the patient response rate to this treatment remains low, especially in patients with cutaneous squamous cell carcinoma (cSCC). 5-Aminoleuvulinic acid-photodynamic therapy (ALA-PDT) is widely used to treat cancerous and precancerous skin diseases, but the value of ALA-PDT in the treatment of invasive cSCC is debatable. Our previous studies have shown that ALA-PDT can induce antitumor immune responses by promoting the immunogenic death of tumor cells. However, it is unclear whether ALA-PDT exerts synergistic effects with ICB in cSCC. Here, we report that PD-L1 blockade potentiates the antitumor effects of ALA-PDT both on primary and distant tumors, and optimizes the tumor microenvironment in cSCC. In this study, we first detected PD-L1 expression in patients with different grades of cSCC. Then we found the combination of anti-PD-L1 monoclonal antibody (mAb) and ALA-PDT killed tumor cells by apoptosis- and/or ferroptosis-mediated immunogenic cell death (ICD) and stimulated systemic immune response, as well as building the immunological memory response to prevent tumor recurrence. Furthermore, we found that combination therapy can be used to recruit tertiary lymphoid structure (TLS)-like intratumoral lymphoid aggregates, which may promote tumor-infiltrating lymphocyte (TIL)-mediated antitumor immunity. In summary, our work demonstrates that ICB treatment with an anti-PD-L1 antibody is a promising strategy that may potentiate the antitumor effects of ALA-PDT in cSCC.

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  • Squamous cancer cells express PD-L1, an immune checkpoint protein that suppresses the T cell function, inhibition of which with an immune checkpoint inhibitor results in synergistic enhancement of the antitumor effect of ALA-PDT.

    “For instance, squamous cancer cells express programmed death-ligand 1 (PD-L1), an immune checkpoint protein that suppresses the T cell function, inhibition of which with an immune checkpoint inhibitor results in synergistic enhancement of the antitumor effect of ALA-PDT [156].”

    From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [156]

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Cited by

Sorted by citations

Authors
Zeng, Q., Yang, J., Ji, J., Wang, P., Zhang, L., Yan, G., Wu, Y., Chen, Q., Liu, J., Zhang, G., & Wang, X.
Affiliations
Tongji University (CN)
Corresponding author
  • Zhang, Guolong
  • Wang, Xiuli
ORCID
Venue
OncoImmunology
Publisher
Informa UK Limited
Published
2022-04-03
Volume
11
Issue
1
Pages
2061396-2061396
ISSN
  • 2162-4011 (ISSN-L)
  • 2162-402X
DOI
10.1080/2162402x.2022.2061396
PMC
PMC8986186
OpenAlex
W4226177259
Cited by
54
References
4
Citations by year
2026: 8 · 2025: 12 · 2024: 15 · 2023: 14 · 2022: 5
FWCI
4.81
Type
journal article
Language
en
Open access
Licence
Locations
  • OncoImmunology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China (No.31801187, 81872212, 82073013)
  • Shanghai Natural Science Foundation (No. 21ZR1457100)
  • Special youth project for clinical research of Shanghai Municipal Health Commission (20194Y0091)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
Keywords
PD-L1 blockade, 5-aminolevulinic acid photodynamic therapy, cutaneous squamous cell carcinoma, immune checkpoint blockade, combination therapy, immunogenic cell death, ferroptosis, tertiary lymphoid structures, tumor-infiltrating lymphocytes, tumor microenvironment, immunological memory, anti-PD-L1 monoclonal antibody
MeSH terms
Carcinoma, Squamous Cell, Humans, Neoplasm Recurrence, Local, Photochemotherapy, Skin Neoplasms, Tumor Microenvironment, B7-H1 Antigen

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