Comparative analyses of tumour immune microenvironment between collecting duct carcinoma and fumarate hydratase-deficient renal cell carcinoma
- 8 November 2022
- journal article
- research article
- Published by BMJ in Journal of Clinical Pathology
- Vol. 77 (2), 105-110
- https://doi.org/10.1136/jcp-2022-208589
Abstract
Aims Collecting duct carcinoma (CDC) and fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) have similar histological morphologies and both show a poor prognosis. Programmed death ligand 1 (PD-L1) inhibitor has been approved for the treatment of RCC. However, tumour-infiltrating neutrophils stimulated by interleukin-8 (IL-8) interfere with PD-L1 inhibitors. Here, we retrospectively analysed PD-L1 and IL-8 expression, and examined its relationship with infiltrating immune cells. Methods Nine cases of CDC and seven cases of FH-deficient RCC were selected. We defined PD-L1 and IL-8 expression by the Tumour Proportion Score and Combined Positive Score (CPS). We counted the numbers of CD8+, CXCR2+, CD11b+, CD66b+ and CD33+ immune cells located in the tumour components. Results A number of CXCR2+ (p=0.0058), CD11b+ (p=0.0070) and CD66b+ (p=0.0067) immune cells infiltrating into CDC were significantly higher than those infiltrating into FH-deficient RCC. In CDC, PD-L1 expression was correlated with a high density of CD8+ lymphocytes (p=0.0389), but was not in FH-deficient RCC (p=0.6985). IL-8 CPS was significantly higher in CDC than in FH-deficient RCC (p=0.0069). In addition, among the CDC cases, IL-8 CPS showed significant positive correlations with CXCR2+, CD11b+ and CD66b+ immune cell densities (p=0.0250, p=0.0104 and p=0.0374, respectively), whereas FH-deficient RCC showed no significant correlations between IL-8 CPS and immune cell densities. Conclusions Our results suggest the difference of each tumour microenvironment between CDC and FH-deficient RCC, and IL-8 is a potential therapeutic target for treating CDC, but not FH-deficient RCC.Keywords
Funding Information
- Fukuoka Public Health Promotion Organization Cancer Research Fund
This publication has 30 references indexed in Scilit:
- Prognostic Role of PD-L1 Expression in Renal Cell Carcinoma. A Systematic Review and Meta-AnalysisTargeted Oncology, 2015
- The prognostic landscape of genes and infiltrating immune cells across human cancersNature Medicine, 2015
- Systemic Therapy for Non–clear Cell Renal Cell Carcinomas: A Systematic Review and Meta-analysisEuropean Urology, 2015
- Tumor-Associated Neutrophils as a New Prognostic Factor in Cancer: A Systematic Review and Meta-AnalysisPLOS ONE, 2014
- Anti-programmed death-1 and anti-programmed death-ligand 1 antibodies in cancer therapyExpert Opinion on Biological Therapy, 2013
- Characteristics and Outcomes of Tumors Arising From the Distal NephronUrology, 2012
- The blockade of immune checkpoints in cancer immunotherapyNature Reviews Cancer, 2012
- The functional significance behind expressing two IL–8 receptor types on PMNJournal of Leukocyte Biology, 2009
- Collecting Duct Renal Cell Carcinoma: A Matched Analysis of 41 CasesEuropean Urology, 2007
- Interleukin-8 and the chemokine familyInternational Journal of Immunopharmacology, 1995