Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
Oncoimmunology. 2022 Apr 3;11(1):2061396. doi: 10.1080/2162402X.2022.2061396. eCollection 2022.
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.
免疫检查点阻断（ICB）是一种针对多种人类恶性肿瘤的强大肿瘤治疗方法，但这种治疗方法的患者应答率仍然较低，尤其是在皮肤鳞状细胞癌（cSCC）患者中。5-氨基酮戊酸-光动力疗法（ALA-PDT）被广泛用于治疗癌症和癌前皮肤病，但 ALA-PDT 在侵袭性 cSCC 治疗中的价值存在争议。我们之前的研究表明，ALA-PDT 通过促进肿瘤细胞的免疫原性死亡来诱导抗肿瘤免疫反应。然而，目前尚不清楚 ALA-PDT 是否与 ICB 在 cSCC 中发挥协同作用。在这里，我们报告 PD-L1 阻断增强了 ALA-PDT 对原发性和远处肿瘤的抗肿瘤作用，并优化了 cSCC 中的肿瘤微环境。在这项研究中，我们首先检测了不同分级 cSCC 患者的 PD-L1 表达。然后我们发现抗 PD-L1 单克隆抗体（mAb）和 ALA-PDT 的组合通过凋亡和/或铁死亡介导的免疫原性细胞死亡（ICD）杀死肿瘤细胞，并刺激全身免疫反应，以及建立免疫记忆反应以防止肿瘤复发。此外，我们发现联合治疗可用于招募三级淋巴结构（TLS）样肿瘤内淋巴聚集物，这可能促进肿瘤浸润淋巴细胞（TIL）介导的抗肿瘤免疫。总之，我们的工作表明，用抗 PD-L1 抗体进行 ICB 治疗可能是一种很有前途的策略，可以增强 ALA-PDT 在 cSCC 中的抗肿瘤作用。
