Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Department of Immunology, Moffitt Cancer Center, Tampa, FL, USA; Cancer Biology PhD Program, University of South Florida, Tampa, FL, USA.
Int Immunopharmacol. 2021 May;94:107481. doi: 10.1016/j.intimp.2021.107481. Epub 2021 Feb 23.
Penile cancer is a rare but highly lethal cancer, and therapeutic options for patients presenting with lymph nodal disease are very limited. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) was shown to provide durable objective response in patients with metastatic melanoma and TIL have been expanded from solid tumors at rates between 70 and 90% depending on the specific diagnosis. We evaluated whether TIL could be expanded from surgical specimens of patients with penile cancer. Tumor samples from metastatic lymph nodes obtained at the time of inguinal lymph node dissection were collected, minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. The phenotype of expanded TILs was assessed by flow cytometry and their anti-tumor reactivity was assessed by IFN-γ ELISA. TIL were expanded from 11 out of 12 (91.6%) samples of metastatic lymph nodes. Expanded TIL were predominantly CD3 (mean 67.5%, SD 19.4%) with a mean of 46.8% CD8 T cells (SD 21.1%). Five out of 11 samples (45.4%) from expanded TIL secreted IFN-γ in response to autologous tumor. TIL expansion and phenotype of expanded T cell lymphocytes were independent of previous HPV infection and treatment with neoadjuvant chemotherapy. This is the first report demonstrating successful expansion of tumor-reactive TIL from penile cancer patients, which support development of ACT strategies using TIL for the treatment of advanced and recurrent penile cancer.
阴茎癌是一种罕见但高度致命的癌症，对于出现淋巴结疾病的患者，治疗选择非常有限。使用肿瘤浸润淋巴细胞（TIL）的过继细胞疗法（ACT）已被证明可在转移性黑色素瘤患者中提供持久的客观缓解，并且根据特定诊断，TIL 已从实体瘤中以 70%至 90%的速率进行了扩展。我们评估了 TIL 是否可以从阴茎癌患者的手术标本中进行扩展。从腹股沟淋巴结清扫术时获得的转移性淋巴结的肿瘤样本被收集，切成小块，放置在 24 孔板的各个孔中，并在高剂量 IL-2 中培养四周。通过流式细胞术评估扩增的 TIL 的表型，并通过 IFN-γ ELISA 评估其抗肿瘤反应性。从 12 个转移性淋巴结样本中的 11 个（91.6%）中扩增了 TIL。扩增的 TIL 主要为 CD3（平均 67.5%，SD 19.4%），平均有 46.8%的 CD8 T 细胞（SD 21.1%）。在 11 个样本中有 5 个（45.4%）从扩增的 TIL 中分泌 IFN-γ 以响应自体肿瘤。TIL 扩增和扩增的 T 细胞淋巴细胞的表型与先前的 HPV 感染和新辅助化疗的治疗无关。这是首次报道成功地从阴茎癌患者中扩增出肿瘤反应性 TIL，这支持了使用 TIL 治疗晚期和复发性阴茎癌的 ACT 策略的发展。
