Jacquelot Nicolas, Roberti María Paula, Enot David P, Rusakiewicz Sylvie, Semeraro Michaela, Jégou Sarah, Flores Camila, Chen Lieping, Kwon Byoung S, Borg Christophe, Weide Benjamin, Aubin François, Dalle Stéphane, Kohrt Holbrook, Ayyoub Maha, Kroemer Guido, Marabelle Aurélien, Cavalcanti Andréa, Eggermont Alexander, Zitvogel Laurence
INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; University Paris Saclay, Kremlin Bicêtre, France; Gustave Roussy Cancer Center, Villejuif, France.
INSERM U1015, Gustave Roussy Cancer Center, Villejuif, France; Gustave Roussy Cancer Center, Villejuif, France; CIC Biothérapie IGR Curie CIC1428, Gustave Roussy Cancer Center, Villejuif, France.
J Invest Dermatol. 2016 May;136(5):994-1001. doi: 10.1016/j.jid.2015.12.042. Epub 2016 Jan 29.
Stage III metastatic melanomas require adequate adjuvant immunotherapy to prevent relapses. Prognostic factors are awaited to optimize the clinical management of these patients. The magnitude of metastatic lymph node invasion and the BRAF(V600) activating mutation have clinical significance. Based on a comprehensive immunophenotyping of 252 parameters per patient in paired blood and metastatic lymph nodes performed in 39 metastatic melanomas, we found that blood markers were as contributive as tumor-infiltrated lymphocyte immunotypes, and parameters associated with lymphocyte exhaustion/suppression showed higher clinical significance than those related to activation or lineage. High frequencies of CD45RA(+)CD4(+) and CD3(-)CD56(-) tumor-infiltrated lymphocytes appear to be independent prognostic factors of short progression-free survival. High NKG2D expression on CD8(+)tumor-infiltrated lymphocytes, low level of regulatory T-cell tumor-infiltrated lymphocytes, and low PD-L1 expression on circulating T cells were retained in the multivariate Cox analysis model to predict prolonged overall survival. Prospective studies are needed to determine whether such immunological markers may guide adjuvant therapies in stage III metastatic melanomas.
III期转移性黑色素瘤需要充分的辅助免疫治疗以预防复发。目前仍在期待能有预后因素来优化这些患者的临床管理。转移性淋巴结浸润的程度以及BRAF(V600)激活突变具有临床意义。基于对39例转移性黑色素瘤患者的配对血液和转移性淋巴结进行的每位患者252项参数的全面免疫表型分析，我们发现血液标志物与肿瘤浸润淋巴细胞免疫类型的贡献相当，并且与淋巴细胞耗竭/抑制相关的参数比与激活或谱系相关的参数具有更高的临床意义。高频率的CD45RA(+)CD4(+)和CD3(-)CD56(-)肿瘤浸润淋巴细胞似乎是无进展生存期短的独立预后因素。在多变量Cox分析模型中，CD8(+)肿瘤浸润淋巴细胞上高表达的NKG2D、肿瘤浸润调节性T细胞的低水平以及循环T细胞上低水平的PD-L1被保留下来以预测延长的总生存期。需要进行前瞻性研究以确定此类免疫标志物是否可指导III期转移性黑色素瘤的辅助治疗。
