Histologic-Based Tumor-Associated Immune Cells Status in Clear Cell Renal Cell Carcinoma Correlates with Gene Signatures Related to Cancer Immunity and Clinical Outcomes
Chisato Ohe,
Takashi Yoshida,
Junichi Ikeda,
Toyonori Tsuzuki,
Riuko Ohashi,
Haruyuki Ohsugi,
Naho Atsumi,
Ryosuke Yamaka,
Ryoichi Saito,
Yoshiki Yasukochi,
Koichiro Higasa,
Hidefumi Kinoshita,
Koji Tsuta
Affiliations
Chisato Ohe
Department of Pathology, Kansai Medical University, Hirakata 573-1191, Japan
Takashi Yoshida
Department of Urology and Andrology, Kansai Medical University, Hirakata 573-1191, Japan
Junichi Ikeda
Department of Pathology, Kansai Medical University, Hirakata 573-1191, Japan
Toyonori Tsuzuki
Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute 480-1195, Japan
Riuko Ohashi
Histopathology Core Facility, Faculty of Medicine, Niigata University, Niigata 951-8510, Japan
Haruyuki Ohsugi
Department of Urology and Andrology, Kansai Medical University, Hirakata 573-1191, Japan
Naho Atsumi
Department of Pathology, Kansai Medical University, Hirakata 573-1191, Japan
Ryosuke Yamaka
Department of Pathology, Kansai Medical University, Hirakata 573-1191, Japan
Ryoichi Saito
Department of Urology and Andrology, Kansai Medical University, Hirakata 573-1191, Japan
Yoshiki Yasukochi
Department of Genome Analysis, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1191, Japan
Koichiro Higasa
Department of Genome Analysis, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1191, Japan
Hidefumi Kinoshita
Department of Urology and Andrology, Kansai Medical University, Hirakata 573-1191, Japan
Koji Tsuta
Department of Pathology, Kansai Medical University, Hirakata 573-1191, Japan
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 (n = 436) and The Cancer Genome Atlas (TCGA)-KIRC cohort (n = 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.
