Histologic-Based Tumor-Associated Immune Cells Status in Clear Cell Renal Cell Carcinoma Correlates with Gene Signatures Related to Cancer Immunity and Clinical Outcomes

• Published in: Biomedicines Vol. 10; no. 2; p. 323
• Main Authors: Ohe, Chisato, Yoshida, Takashi, Ikeda, Junichi, Tsuzuki, Toyonori, Ohashi, Riuko, Ohsugi, Haruyuki, Atsumi, Naho, Yamaka, Ryosuke, Saito, Ryoichi, Yasukochi, Yoshiki, Higasa, Koichiro, Kinoshita, Hidefumi, Tsuta, Koji
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.01.2022; MDPI
• Subjects: Angiogenesis; Antigens; cancer immunity; CD8 antigen; clear cell renal cell carcinoma; Clear cell-type renal cell carcinoma; clinical outcome; Clinical outcomes; Gene expression; gene expression signatures; Genomes; Immunity; Immunohistochemistry; immunophenotype; Immunotherapy; Inflammation; Kidney cancer; Kinases; Medical prognosis; Metastasis; PD-L1 protein; Tumors; Variables; United States > US; Japan; clear cell renal cell carcinoma; cancer immunity; immunohistochemistry; clinical outcome; gene expression signatures; immunophenotype
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10020323

The three-tier immunophenotype (desert, excluded, and inflamed) and the four-tier immunophenotype (cold, immunosuppressed, excluded, and hot) have been linked to prognosis and immunotherapy response. This study aims to evaluate whether immunophenotypes of clear cell renal cell carcinoma, identified on hematoxylin and eosin-stained slides, correlate with gene expression signatures related to cancer immunity, and clinical outcomes. We evaluated tumor-associated immune cells (TAICs) status using three methodologies: three-tier immunophenotype based on the location of TAICs, four-tier immunophenotype considering both the location and degree of TAICs and inflammation score focusing only on the degree of TAICs, using a localized clear cell renal cell carcinoma cohort ( = 436) and The Cancer Genome Atlas (TCGA)-KIRC cohort ( = 162). We evaluated the association of the TAICs status assessed by three methodologies with CD8 and PD-L1 immunohistochemistry and immune gene expression signatures by TCGA RNA-sequencing data. All three methodologies correlated with immunohistochemical and immune gene expression signatures. The inflammation score and the four-tier immunophenotype showed similarly higher accuracy in predicting recurrence-free survival and overall survival compared to the three-tier immunophenotype. In conclusion, a simple histologic assessment of TIACs may predict clinical outcomes and immunotherapy responses.