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.
Antineoplastic Agents
/ therapeutic use
CD8-Positive T-Lymphocytes
/ immunology
Carcinoma, Renal Cell
/ metabolism
Female
Humans
Immunotherapy
/ methods
Interleukin-2
/ therapeutic use
Kidney Neoplasms
/ pathology
Lymphocytes, Tumor-Infiltrating
/ pathology
Male
Middle Aged
Multivariate Analysis
Neoplasm Staging
Predictive Value of Tests
Prognosis
Retrospective Studies
Survival Analysis
Treatment Outcome
beta 2-Microglobulin
/ metabolism
Beta-2-microglobulin
CD8
Clear cell renal cell carcinoma
Immunoscore
Interleukin 2
Outcome
TIL
Tumor infiltrating lymphocyte
Tumor microenvironment
Journal
Annals of diagnostic pathology
ISSN: 1532-8198
Titre abrégé: Ann Diagn Pathol
Pays: United States
ID NLM: 9800503
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
09
04
2020
revised:
29
04
2020
accepted:
16
05
2020
pubmed:
27
5
2020
medline:
23
6
2021
entrez:
27
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32454441
pii: S1092-9134(20)30078-2
doi: 10.1016/j.anndiagpath.2020.151537
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Interleukin-2
0
beta 2-Microglobulin
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
151537Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All authors declare no conflicts of interest and nothing to disclose.