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Comparative analyses of tumour immune microenvironment between collecting duct carcinoma and fumarate hydratase-deficient renal cell carcinoma
  1. Daisuke Kiyozawa1,
  2. Kenichi Kohashi1,
  3. Dai Takamatsu1,
  4. Shinya Umekita1,
  5. Masatoshi Eto2,
  6. Mitsuru Kinjo3,
  7. Kenichi Nishiyama4,
  8. Kenichi Taguchi5,
  9. Yumi Oshiro6,
  10. Yusuke Kuboyama7,
  11. Yoshinao Oda1
  1. 1Department of Anatomic Pathology, Kyushu University, Fukuoka, Japan
  2. 2Department of Urology, Kyushu University, Fukuoka, Japan
  3. 3Department of Pathology, Steel memorial Yawata Hospital, Kitakyushu, Japan
  4. 4Department of Pathology, Fukuoka Red Cross Hospital, Fukuoka, Japan
  5. 5Department of Pathology, National Kyushu Cancer Center, Fukuoka, Japan
  6. 6Department of Pathology, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan
  7. 7Department of Pathology, Oita Red Cross Hospital, Oita, Japan
  1. Correspondence to Professor Yoshinao Oda, Department of Anatomic Pathology, Kyushu University, Fukuoka, Japan; oda.yoshinao.389{at}


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.


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  • Handling editor Runjan Chetty.

  • Contributors DK performed the research and wrote the paper. KK, DT and SU contributed to the research design and slide review. ME, MK, KN, KT, YuO and YK contributed to the sample collection and research design. YoO designed the research and gave final approval of the manuscript. All authors critically reviewed and approved the manuscript. YoO is responsible for the overall content as the guarantor.

  • Funding This study was supported by a Fukuoka Public Health Promotion Organization Cancer Research Fund.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.