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Supplementary Data from Tumor MHC Class I Expression Associates with Intralesional IL2 Response in Melanoma

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posted on 2023-04-04, 01:26 authored by Maryam Pourmaleki, Caitlin J. Jones, Charlotte E. Ariyan, Zheng Zeng, Mono Pirun, Daniel A. Navarrete, Yanyun Li, Mianlei Zhang, Subhiksha Nandakumar, Carl Campos, Saad Nadeem, David S. Klimstra, Claire F. Temple-Oberle, Thomas Brenn, Evan J. Lipson, Kara M. Schenk, Julie E. Stein, Janis M. Taube, Michael G. White, Raymond Traweek, Jennifer A. Wargo, John M. Kirkwood, Billel Gasmi, Stephanie L. Goff, Alex D. Corwin, Elizabeth McDonough, Fiona Ginty, Margaret K. Callahan, Andrea Schietinger, Nicholas D. Socci, Ingo K. Mellinghoff, Travis J. Hollmann
Supplementary Data from Tumor MHC Class I Expression Associates with Intralesional IL2 Response in Melanoma

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NIH

American Association for Cancer Research

MD Anderson

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ARTICLE ABSTRACT

Cancer immunotherapy can result in lasting tumor regression, but predictive biomarkers of treatment response remain ill-defined. Here, we performed single-cell proteomics, transcriptomics, and genomics on matched untreated and IL2 injected metastases from patients with melanoma. Lesions that completely regressed following intralesional IL2 harbored increased fractions and densities of nonproliferating CD8+ T cells lacking expression of PD-1, LAG-3, and TIM-3 (PD-1−LAG-3−TIM-3−). Untreated lesions from patients who subsequently responded with complete eradication of all tumor cells in all injected lesions (individuals referred to herein as “extreme responders”) were characterized by proliferating CD8+ T cells with an exhausted phenotype (PD-1+LAG-3+TIM-3+), stromal B-cell aggregates, and expression of IFNγ and IL2 response genes. Loss of membranous MHC class I expression in tumor cells of untreated lesions was associated with resistance to IL2 therapy. We validated this finding in an independent cohort of metastatic melanoma patients treated with intralesional or systemic IL2. Our study suggests that intact tumor-cell antigen presentation is required for melanoma response to IL2 and describes a multidimensional and spatial approach to develop immuno-oncology biomarker hypotheses using routinely collected clinical biospecimens.

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    Cancer Immunology Research

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