Studies have reported the relevance of immune phenotype, or presence of cluster of differentiation 8 (CD8)-positive tumour-infiltrating lymphocytes, to the anti-tumour efficacy of checkpoint inhibitors and to prognosis. The multicentre, retrospective ARCHERY study (UMIN000034131) collected tissue samples from Japanese patients with recurrent or metastatic renal cell carcinoma (RCC) who received systemic therapy between 2010 and 2015. In this exploratory analysis, the prognostic impact of immune phenotype and PD-L1 expression (separately and combined) was investigated using 770 surgical specimens and outcomes from patients enrolled in ARCHERY. A key objective was to determine overall survival (OS), defined as time from nephrectomy to death from any cause, by immune and PD-L1 subgroups. The median OS by immune phenotype was 28.8, 57.3, and 63.4 months in patients with inflamed, excluded, and desert tumours, respectively [hazard ratio (95% CI): inflamed 1.78 (1.27-2.49); excluded 1.08 (0.89-1.30); desert as reference]. PD-L1 positivity by SP142 showed a strong association with immune phenotype; 88.1%, 61.9%, and 8.7% of PD-L1-positive patients had inflamed, excluded, and desert phenotypes, respectively. PD-L1 positivity was also associated with worse OS in each phenotype, except for the inflamed phenotype (due to limited sample size in the PD-L1-negative immune inflamed subgroup; n=7). Additionally, the difference in OS by PD-L1 status was larger in the desert versus excluded phenotype [median OS in PD-L1 positive vs negative: 27.1 vs 67.2 months (desert), and 48.2 vs 78.1 months (excluded)]. Results show that PD-L1 expression was highly associated with immune phenotype, but both covariates should be evaluated when determining prognosis.
Pathology. 2022 Sep 20 [Epub ahead of print]
Toyonori Tsuzuki, Chisato Ohe, Takahiro Osawa, Yosuke Yasuda, Toshiaki Tanaka, Satoshi Anai, Go Kimura, Kazutoshi Yamana, Shingo Hatakeyama, Takuya Yoshimoto, Yuki Nakagawa, Tamaki Fukuyama, Nobuaki Matsubara, Hirotsugu Uemura
Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Aichi, Japan., Department of Pathology, Kansai Medical University, Hirakata, Osaka, Japan. Electronic address: ., Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan., Department of Urology, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo, Japan., Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan., Department of Urology, Nara Medical University, Kashihara-shi, Nara, Japan., Department of Urology, Nippon Medical School, Bunkyo-ku, Tokyo, Japan., Department of Urology, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi, Niigata, Japan., Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan., Clinical Development Division, Chugai Pharmaceutical Co., Ltd., Chuo-ku, Tokyo, Japan., Medical Affairs Division, Chugai Pharmaceutical Co., Ltd., Chuo-ku, Tokyo, Japan., Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa-shi, Chiba-ken, Japan., Department of Urology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan.