Synapse - Tumor MHC class I expression associates with intralesional IL2 response in melanoma

Tumor MHC class I expression associates with intralesional IL2 response in melanoma Journal Article

Authors:	Pourmaleki, M.; Jones, C. J.; Ariyan, C. E.; Zeng, Z.; Pirun, M.; Navarrete, D. A.; Li, Y.; Zhang, M.; Nandakumar, S.; Campos, C.; Nadeem, S.; Klimstra, D. S.; Temple-Oberle, C. F.; Brenn, T.; Lipson, E. J.; Schenk, K. M.; Stein, J. E.; Taube, J. M.; White, M. G.; Traweek, R.; Wargo, J. A.; Kirkwood, J. M.; Gasmi, B.; Goff, S. L.; Corwin, A. D.; McDonough, E.; Ginty, F.; Callahan, M. K.; Schietinger, A.; Socci, N. D.; Mellinghoff, I. K.; Hollmann, T. J.
Article Title:	Tumor MHC class I expression associates with intralesional IL2 response in melanoma
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. ©2022 American Association for Cancer Research.
Journal Title:	Cancer Immunology Research
Volume:	10
Issue:	3
ISSN:	2326-6066
Publisher:	American Association for Cancer Research
Date Published:	2022-03-01
Start Page:	303
End Page:	313
Language:	English
DOI:	10.1158/2326-6066.Cir-21-1083
PUBMED:	35013003
PROVIDER:	scopus
PMCID:	PMC8898286
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85125883287&doi=10.1158%2f2326-6066.CIR-21-1083&partnerID=40&md5=065be8efd108471013ed3e834479c3d6
Notes:	Article -- Export Date: 1 April 2022 -- Source: Scopus