Department of Dermatology, University Hospital of Besancon, Besancon, France; INSERM, EFS BFC, UMR1098, RIGHT, University of Burgundy Franche-Comte, Besancon, France.
INSERM, EFS BFC, UMR1098, RIGHT, University of Burgundy Franche-Comte, Besancon, France; INSERM CIC 1431, Clinical Investigation Center in Biotherapy, Biomonitoring Plateform, Besancon, France.
J Invest Dermatol. 2022 Feb;142(2):435-444. doi: 10.1016/j.jid.2021.07.160. Epub 2021 Aug 2.
CD4 T cells play a key role in anticancer immunity. In this study, we investigate the clinical relevance of circulating CD4 T helper type 1 (Th1) response against telomerase (anti-TERT Th1 response) in patients with melanoma. The spontaneous anti-TERT Th1 response was detected in 54.5% (85/156) of patients with melanoma before treatment. The prevalence of this systemic response was inversely related to Breslow thickness >1 mm and American Joint Committee on Cancer stage ≥II (P = 0.001 and 0.032, respectively). In contrast to patients treated with targeted therapies, the anti-TERT Th1 immunity was associated with an objective response after immune checkpoint inhibitors treatment. Hence, 86% (18/21) of responder patients exhibited pre-existing anti-TERT Th1 versus 35% (6/19) in nonresponders (P = 0.001). This response was also associated with increased progression-free survival and overall survival in patients with melanoma treated with immune checkpoint inhibitors (P = 0.0008 and 0.012, respectively). Collectively, the presence of circulating anti-TERT Th1 response is inversely related to melanoma evolution and appears to be a predictive factor of response to immunotherapy. Our results highlight the interest in telomerase-specific CD4 Th1 response as a promising blood-based biomarker of immune checkpoint inhibitors therapy in melanoma.
CD4 T 细胞在抗肿瘤免疫中发挥着关键作用。在这项研究中，我们研究了循环 CD4 辅助性 T 细胞 1（Th1）对端粒酶（抗 TERT Th1 反应）的临床相关性在黑色素瘤患者中。在治疗前，54.5%（85/156）的黑色素瘤患者检测到自发的抗 TERT Th1 反应。这种全身性反应的流行率与 Breslow 厚度>1mm 和美国癌症联合委员会分期≥II 呈负相关（P 值分别为 0.001 和 0.032）。与接受靶向治疗的患者相比，抗 TERT Th1 免疫与免疫检查点抑制剂治疗后的客观反应相关。因此，在应答患者中，86%（18/21）的患者存在预先存在的抗 TERT Th1，而在无应答患者中为 35%（6/19）（P 值=0.001）。这种反应也与接受免疫检查点抑制剂治疗的黑色素瘤患者的无进展生存期和总生存期延长相关（P 值分别为 0.0008 和 0.012）。总之，循环抗 TERT Th1 反应的存在与黑色素瘤的发生呈负相关，并且似乎是对免疫治疗反应的预测因素。我们的研究结果强调了端粒酶特异性 CD4 Th1 反应作为黑色素瘤免疫检查点抑制剂治疗有前途的基于血液的生物标志物的重要性。
