Comparative analyses of tumour immune microenvironment between collecting duct carcinoma and fumarate hydratase-deficient renal cell carcinoma

• Published in: Journal of clinical pathology Vol. 77; no. 2; p. 105
• Main Authors: Kiyozawa, Daisuke, Kohashi, Kenichi, Takamatsu, Dai, Umekita, Shinya, Eto, Masatoshi, Kinjo, Mitsuru, Nishiyama, Kenichi, Taguchi, Kenichi, Oshiro, Yumi, Kuboyama, Yusuke, Oda, Yoshinao
• Format: Journal Article
• Language: English
• Published: England 01-02-2024
• Subjects: B7-H1 Antigen; Carcinoma, Renal Cell - pathology; Fumarate Hydratase; Humans; Interleukin-8; Kidney Neoplasms - pathology; Retrospective Studies; Tumor Microenvironment; KIDNEY; CARCINOMA; IMMUNOHISTOCHEMISTRY
• ISSN: 1472-4146
• DOI: 10.1136/jcp-2022-208589

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.
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.
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.
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.