Qin Yong, Petaccia de Macedo Mariana, Reuben Alexandre, Forget Marie-Andrée, Haymaker Cara, Bernatchez Chantale, Spencer Christine N, Gopalakrishnan Vancheswaran, Reddy Sujan, Cooper Zachary A, Fulbright Orenthial J, Ramachandran Renjith, Wahl Arely, Flores Esteban, Thorsen Shawne T, Tavera Rene J, Conrad Claudius, Williams Michelle D, Tetzlaff Michael T, Wang Wei-Lien, Gombos Dan S, Esmaeli Bita, Amaria Rodabe N, Hwu Patrick, Wargo Jennifer A, Lazar Alexander J, Patel Sapna P
Department of Melanoma Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Oncoimmunology. 2017 May 8;6(6):e1321187. doi: 10.1080/2162402X.2017.1321187. eCollection 2017.
The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8 T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.
葡萄膜黑色素瘤（UM）对免疫疗法的低反应率与皮肤黑色素瘤（CM）患者可观的反应率形成鲜明对比。为了阐明UM对免疫疗法耐药的机制，我们通过免疫组织化学（IHC）对10例转移性UM患者和10例转移性CM患者的肿瘤进行了免疫分析。尽管UM和CM之间浸润性CD8 T细胞没有差异，但观察到程序性死亡-1（PD-1）阳性淋巴细胞显著减少，且与CM转移灶相比，UM转移灶中程序性死亡配体-1（PD-L1）水平较低。与转移性CM相比，转移性UM患者的肿瘤浸润淋巴细胞（TIL）生长成功率较低（45%对64%），总体上UM TIL扩增数量显著较少。这些研究表明，UM和CM在免疫方面存在差异，并为UM免疫疗法效果不佳提供了潜在解释。
