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Review
. 2024 Nov 30;13(11):6565-6575.
doi: 10.21037/tcr-24-742. Epub 2024 Nov 6.

Immunotherapy for locally advanced and metastatic basal cell carcinoma: a narrative review

Xiaoqing Li  1   2 , Hongru Wang  1 , Qingli Lu  2   3
Affiliations
Review

Immunotherapy for locally advanced and metastatic basal cell carcinoma: a narrative review

Xiaoqing Li et al. Transl Cancer Res. .

Abstract

Background and objective: Basal cell carcinoma (BCC) is the most common malignancy of humankind, characterized by its low propensity for metastasis and its high recurrence rate. Surgical intervention is the predominant therapeutic approach. However, for cases of locally advanced BCC (laBCC) and metastatic BCC (mBCC), systematic therapy may be the first option. In recent years, tumor immunotherapy has garnered significant attention within the scientific community. And it has progressively demonstrated its efficacy in the treatment of laBCC and mBCC. This review aims to summarize the characteristics of immune microenvironment, biomarkers, and immunotherapies of BCC, and provide a reference for further research on BCC immunotherapy.

Methods: We searched literature in PubMed database and Web of Science and considered all study types written in English from 2013 to 2024.

Key content and findings: The alteration of the immune microenvironment is a pivotal factor in the progression of BCC. The expression levels of sex determining region Y (SRY)-box 2 (SOX2) and matrix metalloproteinases (MMPs) have emerged as potential prognostic biomarkers for BCC. And they are promising therapeutic targets for laBCC and mBCC. For patients presenting with laBCC or mBCC, a spectrum of immunotherapeutic approaches is being explored, including inhibition of the programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1), blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activation gene 3 (LAG-3) inhibition therapy, the use of chimeric antigen receptor (CAR)-T cells, and vaccination. Cemiplimab is the first immune checkpoint inhibitor (ICI) approved by the Food and Drug Administration for refractory BCC, marking a major breakthrough in BCC immunotherapy.

Conclusions: Immunotherapies have shown efficacy in clinical studies. In the future, more multicenter studies with large samples are needed to further explore the efficacy and safety of immunotherapy for BCC.

Keywords: Basal cell carcinoma (BCC); biomarker; immune checkpoint inhibitor (ICI); immune microenvironment; immunotherapy.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-742/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Immune microenvironment of BCC. Signal 1: CD80/CD86 combines with CTLA-4 and then inhibit TIL activation; signal 2: PD-1 combines with PD-L1 and then inhibits the host immune response and results in TIL exhaustion and apoptosis. APC, antigen-presenting cell; TIL, tumor-infiltrating lymphocyte; CAF, cancer-associated fibroblast; TAM, tumor-associated macrophage; CTLA-4, cytotoxic T-lymphocyte antigen 4; LAG-3, lymphocyte activation gene 3; PD-1, programmed death receptor 1; PD-L1, programmed death ligand 1; BCC, basal cell carcinoma.
Figure 2
Figure 2
Targeting therapy of BCC. Signal 1: CD80/CD86 combines with CTLA-4 and then inhibit TIL activation; signal 2: PD-1 combines with PD-L1 and then inhibits the host immune response and results in TIL exhaustion and apoptosis, APC, antigen-presenting cell; TIL, tumor-infiltrating lymphocyte; CAF, cancer-associated fibroblast; TAM, tumor-associated macrophage; CTLA-4, cytotoxic T-lymphocyte antigen 4; LAG-3, lymphocyte activation gene 3; PD-1, programmed death receptor 1; PD-L1, programmed death ligand 1; CAR-T, chimeric antigen receptor-T; BCC, basal cell carcinoma.
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