Long-term survival and clinical benefit from adoptive T-cell transfer in stage IV melanoma patients is determined by a four-parameter tumor immune signature
Menée sur des métastases issues de 73 patients atteints d'un mélanome de stade IV et à l'aide des données du projet "The Cancer Genome Atlas", cette étude identifie une signature, basée sur 4 paramètres associés à l'immunité tumorale (concentration de lymphocytes T CD8+, expression de galectine-3 par les cellules tumorales, ... ), pour prédire la survie à long terme des patients et la réponse à un traitement par transfert adoptif de lymphocytes T
The presence of tumor-infiltrating immune cells is associated with longer survival and a better response to immunotherapy in early stage melanoma, but a comprehensive study of the in situ immune microenvironment in stage IV melanoma has not been performed. We investigated the combined influence of a series of immune factors on survival and response to adoptive cell transfer (ACT) in stage IV melanoma patients. Metastases of 73 stage IV melanoma patients, 17 of which were treated with ACT, were studied with respect to the number and functional phenotype of lymphocytes and myeloid cells as well as for expression of galectins-1, -3, and -9. Single factors associated with better survival were identified using Kaplan-Meier curves and multivariate Cox regression analyzes and those factors were used for interaction analyses. The results were validated using The Cancer Genome Atlas (TCGA) database. We identified four parameters that were associated with a better survival: CD8+ T cells, galectin-9+ DCs/DC-like macrophages, a high M1/M2 macrophage ratio and the expression of galectin-3 by tumor cells. The presence of at least three of these parameters formed an independent positive prognostic factor for long-term survival. Patients displaying this four-parameter signature were found exclusively among patients responding to ACT and were the ones with sustained clinical benefit.
Cancer Immunology Research , résumé, 2016