Abundant CD8+ tumor infiltrating lymphocytes and beta-2-microglobulin are associated with better outcome and response to interleukin-2 therapy in advanced stage clear cell renal cell carcinoma.

Autor: Davis D; Oregon Health & Science University, Department of Pathology, Portland, OR 97239, United States of America., Tretiakova MS; University of Washington, Department of Pathology, Seattle, WA 98195, United States of America., Kizzar C; Oregon Health & Science University, Department of Pathology, Portland, OR 97239, United States of America., Woltjer R; Oregon Health & Science University, Department of Pathology, Portland, OR 97239, United States of America., Krajbich V; Oregon Health & Science University, Department of Pathology, Portland, OR 97239, United States of America., Tykodi SS; University of Washington, Department of Medicine, Division of Medical Oncology, Seattle, WA 98109, United States of America; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States of America., Lanciault C; Oregon Health & Science University, Department of Pathology, Portland, OR 97239, United States of America., Andeen NK; Oregon Health & Science University, Department of Pathology, Portland, OR 97239, United States of America. Electronic address: andeen@ohsu.edu.
Jazyk: angličtina
Zdroj: Annals of diagnostic pathology [Ann Diagn Pathol] 2020 Aug; Vol. 47, pp. 151537. Date of Electronic Publication: 2020 May 19.
DOI: 10.1016/j.anndiagpath.2020.151537
Abstrakt: Studies assessing tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC) and clinical outcomes have mixed results. Given fundamental interaction of MHC class I with CD8+ T-cells, we hypothesized that expression of MHC class I associated protein, beta-2-microglobulin (B2M), may be an important immunologic marker in RCC. We sought to understand potential implications of CD8 + TILs and tumor B2M expression on overall survival and response to high-dose interleukin-2 (IL-2) therapy, in a cohort of patients with high-stage (clinical stage III and IV) ccRCC. Four tumor regions from 56 patients with ccRCC were retrospectively assessed immunohistochemically. At a median follow-up time of 33 months, 22 (39%) patients had died of disease, 23 (41%) were alive disease, and 11 (20%) had no evidence of disease. Tumors with high CD8 + TILs had a significantly lower death rate [hazard ratio (HR): 0.33, p = 0.02]. CD8 + TILs correlated with B2M expression (p = 0.007). On multivariable analyses, patients with both high B2M and CD8 + TILs had lower death rate (HR: 0.27, p = 0.03). Within the subgroup treated with IL-2 (n = 27, 48%), tumors with high CD8 + TILs were more likely to respond to IL-2 therapy [coefficient (coef): 1.6, p = 0.05]. On multivariable analyses, tumors with a combination of both high B2M expression and high CD8 + TILs also showed trend to responding to IL-2 therapy (coef: 2.5, p = 0.06). In conclusion, abundant CD8+ TILs and high tumor expression of beta-2-microglobulin were good prognostic indicators associated with longer survival in patients with high-stage ccRCC. Abundant CD8+ TILs may predict response to IL-2 therapy.
Competing Interests: Declaration of competing interest All authors declare no conflicts of interest and nothing to disclose.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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