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Immune Phenotype-Genotype Associations in Primary Clear Cell Renal Cell Carcinoma and Matched Metastatic Tissue.
Sobottka, Bettina; Vetter, Viola; Banaei-Esfahani, Amir; Nowak, Marta; Lorch, Anja; Sirek, Andrej; Mertz, Kirsten D; Brunelli, Matteo; Berthold, Dominik; de Leval, Laurence; Kahraman, Abdullah; Koelzer, Viktor Hendrik; Moch, Holger.
Afiliación
  • Sobottka B; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address: annabettina.sobottka-brillout@usz.ch.
  • Vetter V; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Banaei-Esfahani A; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Nowak M; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
  • Lorch A; Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland.
  • Sirek A; Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
  • Mertz KD; Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland; Institute of Medical Genetics and Pathology, University Hospital of Basel, Basel, Switzerland.
  • Brunelli M; Università di Verona, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.
  • Berthold D; Department of Oncology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland.
  • de Leval L; Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland.
  • Kahraman A; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; School of Life Sciences Fachhochschule Nordwestschweiz, Institute for Chemistry and Bioanalytics, Muttenz, Switzerland.
  • Koelzer VH; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute of Medical Genetics and Pathology, University Hospital of Basel, Basel, Switzerland.
  • Moch H; Department of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Mod Pathol ; 37(10): 100558, 2024 Jul 04.
Article en En | MEDLINE | ID: mdl-38969270
ABSTRACT
Adjuvant immunotherapy has been recently recommended for patients with metastatic clear cell renal cell carcinoma (ccRCC), but there are no tissue biomarkers to predict treatment response in ccRCC. Potential predictive biomarkers are mainly assessed in primary tumor tissue, whereas metastases (METs) remain understudied. To explore potential differences between genomic alterations and immune phenotypes in primary tumors and their matched METs, we analyzed primary tumors (PTs) of 47 ccRCC patients and their matched distant METs by comprehensive targeted parallel sequencing, whole-genome copy number variation analysis, determination of microsatellite instability, and tumor mutational burden. We quantified the spatial distribution of tumor-infiltrating CD8+ T cells and coexpression of the T-cell-exhaustion marker thymocyte selection-associated high mobility group box (TOX) by digital immunoprofiling and quantified tertiary lymphoid structures. Most METs were pathologically "cold." Inflamed, pathologically "hot" PTs were associated with decreased disease-free survival, worst for patients with high levels of CD8+TOX+ T cells. Interestingly, inflamed METs showed a relative increase in exhausted CD8+TOX+ T cells and increased accumulative size of tertiary lymphoid structures compared with PTs. Integrative analysis of molecular and immune phenotypes revealed BAP1 and CDKN2A/B deficiency to be associated with an inflamed immune phenotype. Our results highlight the distinct spatial distribution and differentiation of CD8+ T cells at metastatic sites, and the association of an inflamed microenvironment with specific genomic alterations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mod Pathol Asunto de la revista: PATOLOGIA Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Mod Pathol Asunto de la revista: PATOLOGIA Año: 2024 Tipo del documento: Article
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