Skin-Test Infiltrating Lymphocytes Early Predict Clinical Outcome of Dendritic Cell-Based Vaccination in Metastatic Melanoma
- 30 November 2012
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 72 (23), 6102-6110
- https://doi.org/10.1158/0008-5472.CAN-12-2479
Abstract
The identification of responding patients early during treatment would improve the capability to develop effective new immunotherapies more rapidly. Here, we describe a bioassay that may link early T-cell-mediated immune responses to later clinical benefits. This bioassay rests upon the tenet of immunotherapy that tumor-specific effector T cells capable of invading peripheral tissue can recognize tumor antigens and exert cytotoxic functions there. To show its utility, we conducted a retrospective study of a large cohort of metastatic melanoma patients (n = 91) enrolled in dendritic cell (DC)-based vaccination protocols to examine a hypothesized correlation of posttreatment skin-infiltrating lymphocytes (SKIL) with overall survival (OS). Stringent immunologic criteria were defined to identify long-term survivors. The presence of tumor-associated antigen (TAA)-specific CD8(+) T cell populations within SKILs (criterion I) was highly predictive for long-term survival. Further restriction by selecting for the presence of TAA-specific CD8(+) T cells specifically recognizing tumor peptide (criterion II) was also associated with improved OS. Recognition of naturally processed antigen (criterion III) maximized the accuracy of the test, with a median OS of 24.1 versus 9.9 months (P = 0.001). Our results show that detailed characterization of SKILs can permit an accurate selection of metastatic melanoma patients who benefit most from DC-based vaccination. This simple and robust bioassay integrates multiple aspects of cellular functions that mediate effective immune responses, thereby offering an effective tool to rapidly identify patients who are responding to immunotherapy at an early stage of treatment. Cancer Res; 72(23); 6102-10. (C) 2012 AACR.Keywords
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This publication has 27 references indexed in Scilit:
- T cell trafficking and metabolism: novel mechanisms and targets for immunomodulationCurrent Opinion in Pharmacology, 2012
- Humoral anti-KLH responses in cancer patients treated with dendritic cell-based immunotherapy are dictated by different vaccination parametersCancer Immunology, Immunotherapy, 2012
- Cancer Immunotherapy Comes of AgeJournal of Clinical Oncology, 2011
- Novel cancer immunotherapy agents with survival benefit: recent successes and next stepsNature Reviews Cancer, 2011
- Cancer immunotherapy – revisitedNature Reviews Drug Discovery, 2011
- Recent Developments in Cancer VaccinesThe Journal of Immunology, 2011
- Guidelines for the Evaluation of Immune Therapy Activity in Solid Tumors: Immune-Related Response CriteriaClinical Cancer Research, 2009
- Harmonization guidelines for HLA-peptide multimer assays derived from results of a large scale international proficiency panel of the Cancer Vaccine ConsortiumCancer Immunology, Immunotherapy, 2009
- Results and harmonization guidelines from two large-scale international Elispot proficiency panels conducted by the Cancer Vaccine Consortium (CVC/SVI)Cancer Immunology, Immunotherapy, 2007
- Gene profiling of immune responses against tumorsCurrent Opinion in Immunology, 2005