Department of Oncology and Hematology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
Department of Oncology and Hematology, Hospital Grabs, Grabs, Switzerland.
Cancer Immunol Immunother. 2018 Jan;67(1):39-45. doi: 10.1007/s00262-017-2061-4. Epub 2017 Sep 11.
Prognosis of metastatic melanoma improved with the development of checkpoint inhibitors. The role of tumor infiltrating lymphocytes (TILs) in lymph node metastases of stage III melanoma remains unclear. We retrospectively characterized TILs in primary melanomas and matched lymph node metastases (stage III melanoma) of patients treated with the checkpoint inhibitor ipilimumab. Tumor infiltrating lymphocytes were characterized for CD3, CD4, and CD8 expressions by immunohistochemistry. 4/9 patients (44%) responded to treatment with ipilimumab (1 complete and 2 partial remissions, 1 stable disease). All responders exhibited CD4 and CD8 T-cell infiltration in their lymph node metastases, whereas all non-responders did not show an infiltration of the lymph node metastasis with TILs. The correlation between the presence and absence of TILs in responders vs. non-responders was statistically significant (p = 0.008). Median distant metastases free survival, i.e., progression from stage III to stage IV melanoma, was similar in responders and non-responders (22.1 vs. 19.3 months; p = 0.462). Median progression free and overall survival show a trend in favor of the patients having TIL rich lymph node metastases (6.8 vs. 3.3 months, p = 0.09; and all alive at last follow-up vs. 8.2 months, respectively, p = 0.08). Our data suggest a correlation between the T-cell infiltration of the lymph node metastases in stage III melanoma and the response to ipilimumab once these patients progress to stage IV disease.
检查点抑制剂的发展改善了转移性黑色素瘤的预后。肿瘤浸润淋巴细胞(TILs)在 III 期黑色素瘤淋巴结转移中的作用仍不清楚。我们回顾性地描述了接受检查点抑制剂伊匹单抗治疗的 III 期黑色素瘤患者的原发黑色素瘤和匹配的淋巴结转移(III 期黑色素瘤)中的 TILs。通过免疫组织化学检测 CD3、CD4 和 CD8 的表达来描述肿瘤浸润淋巴细胞。4/9 名患者(44%)对伊匹单抗治疗有反应(1 例完全缓解,2 例部分缓解,1 例疾病稳定)。所有应答者的淋巴结转移中均存在 CD4 和 CD8 T 细胞浸润,而所有无应答者的淋巴结转移中均未观察到 TIL 浸润。应答者与无应答者 TIL 存在与否的相关性具有统计学意义(p=0.008)。从 III 期到 IV 期黑色素瘤的远处无转移生存(即进展)的中位数在应答者和无应答者之间相似(22.1 与 19.3 个月;p=0.462)。无进展生存和总生存的中位数倾向于 TIL 丰富的淋巴结转移患者(6.8 与 3.3 个月,p=0.09;最后一次随访时均存活,分别为 8.2 个月,p=0.08)。我们的数据表明,III 期黑色素瘤淋巴结转移中的 T 细胞浸润与这些患者进展为 IV 期疾病后对伊匹单抗的反应之间存在相关性。