Daiki Ikarashi1,2,3, Shigehisa Kitano4, Takashi Tsuyukubo1, Kazumasa Takenouchi3, Takayuki Nakayama3, Hiroko Onagi5, Asumi Sakaguchi5, Makiko Yamashita2, Hidenori Mizugaki2, Shigekatsu Maekawa1, Renpei Kato1, Yoichiro Kato1, Tamotsu Sugai6, Tetsuya Nakatsura3, Wataru Obara1. 1. Department of Urology, Iwate Medical University School of Medicine, Iwate, 028-3695, Japan. 2. Division of Cancer Immunotherapy Development, Advanced Medical Development Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan. 3. Division of Cancer Immunotherapy, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Chiba, 277-0872, Japan. 4. Division of Cancer Immunotherapy Development, Advanced Medical Development Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan. shigehisa.kitano@jfcr.or.jp. 5. Department of Human Pathology, Juntendo University School of Medicine, Tokyo, 113-0033, Japan. 6. Department of Pathology, Iwate Medical University School of Medicine, Iwate, 028-3695, Japan.
Abstract
BACKGROUND: We examined the relationship between the tumour microenvironment and the clinical efficacy of neoadjuvant chemotherapy in patients with cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. METHODS: The study retrospectively evaluated 51 patients who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. Patients were divided into responders (<pT2) and non-responders (≥pT2). We assessed the density of each immune cell type in intratumoural and peritumoural areas in both groups via multiplex fluorescence immunohistochemical analysis. RESULTS: The median age was 69 years; 39 patients were male. Twelve (23.5%), 17 (33.3%), 10 (19.7%) and 12 (23.5%) patients were pT0, pT1, pT2 and ≥pT3, respectively. Responders had a significantly higher 5-year cancer-specific survival rate (96.6%) than non-responders (48.4%; p = 0.0018). CD8+ T cell (p = 0.0056) and CD204+ cell (p = 0.0394) densities were significantly higher in the intratumoural area in non-responders than in responders. Patients with higher CD204+ cell densities in cancerous areas had worse prognosis. CONCLUSIONS: This comprehensive analysis of the immune microenvironment of a muscle-invasive bladder cancer specimen revealed that preexisting tumour-infiltrating proliferating CD8+ T cells and CD204+ cells are indicators of the response to neoadjuvant chemotherapy and that CD204+ cells can be considered an unfavourable prognostic factor in these patients.
BACKGROUND: We examined the relationship between the tumour microenvironment and the clinical efficacy of neoadjuvant chemotherapy in patients with cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. METHODS: The study retrospectively evaluated 51 patients who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. Patients were divided into responders (<pT2) and non-responders (≥pT2). We assessed the density of each immune cell type in intratumoural and peritumoural areas in both groups via multiplex fluorescence immunohistochemical analysis. RESULTS: The median age was 69 years; 39 patients were male. Twelve (23.5%), 17 (33.3%), 10 (19.7%) and 12 (23.5%) patients were pT0, pT1, pT2 and ≥pT3, respectively. Responders had a significantly higher 5-year cancer-specific survival rate (96.6%) than non-responders (48.4%; p = 0.0018). CD8+ T cell (p = 0.0056) and CD204+ cell (p = 0.0394) densities were significantly higher in the intratumoural area in non-responders than in responders. Patients with higher CD204+ cell densities in cancerous areas had worse prognosis. CONCLUSIONS: This comprehensive analysis of the immune microenvironment of a muscle-invasive bladder cancer specimen revealed that preexisting tumour-infiltrating proliferating CD8+ T cells and CD204+ cells are indicators of the response to neoadjuvant chemotherapy and that CD204+ cells can be considered an unfavourable prognostic factor in these patients.
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