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Research ArticleExperimental Studies

Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment

ZHENLONG ZHENG, DAE SAN YOO, SHANSHAN LI, MEILING PEI, SANG GYUN LEE, JI YOUNG KIM, KEE YANG CHUNG and MI RYUNG ROH
Anticancer Research September 2022, 42 (9) 4359-4369; DOI: https://doi.org/10.21873/anticanres.15936
ZHENLONG ZHENG
1Department of Dermatology, Yanbian University Hospital, Yanji, P.R. China;
2Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea;
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DAE SAN YOO
3Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea;
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SHANSHAN LI
4Department of Pathology, Yanbian University Hospital, Yanji, P.R. China;
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MEILING PEI
2Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea;
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SANG GYUN LEE
3Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea;
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JI YOUNG KIM
5Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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KEE YANG CHUNG
2Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea;
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MI RYUNG ROH
3Department of Dermatology, Gangnam Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea;
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  • For correspondence: karenroh@yuhs.ac
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Abstract

Background/Aim: The role of cancer-associated fibroblasts (CAFs) in the pathogenesis of Merkel cell carcinoma (MCC) remains unknown. This study aimed to investigate the clinicopathological significance of CAF subpopulations and their association with tumor-infiltrating lymphocytes (TILs) in patients with MCC. Materials and Methods: Clinicopathological features and the status of microenvironment fibrosis (MF) around tumor masses were evaluated in 20 MCC patient and tissue sections. Alpha-smooth muscle actin (α-SMA)-positive CAFs (α-SMA+CAFs), interleukin-6-positive CAFs (IL6+CAFs), CD4-positive TILs (CD4+TILs), and CD8-positive TILs (CD8+TILs) in MCC tissue samples were investigated using immunohistochemistry. Results: In a total of 20 MCC patients, high-MF was detected in 12 (60%) patients which was significantly associated with worse progression-free survival (p=0.048), but not with overall survival. CD4+/CD8+ TILs were frequently detected in MCC tissues. High-intra-tumoral CD8+TIL was significantly associated with better overall and progression-free survival (p=0.04 and p=0.015) in our cohort. High-αSMA+ CAFs were detected in 11 (55.0%) patients and high-IL6+CAFs in 10 (50.0%) patients. A negative association was found between high-IL6+CAF and high-intra-tumoral CD8+TILs (p=0.005). Patients with high IL6+CAFs showed worse overall/progression-free survival than patients with low-IL6+CAFs (p=0.022 and p=0.035). Conclusion: IL6+CAFs may largely influence the tumor immune microenvironment of MCC by modulating distinct T-cell populations and functions. This study provides a possible therapeutic target to overcome resistance to immune therapies in MCC.

Key Words:
  • Merkel cell carcinoma
  • tumor infiltrating lymphocytes
  • cancer-associated fibroblasts
  • Received June 25, 2022.
  • Revision received July 19, 2022.
  • Accepted July 20, 2022.
  • Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 42 (9)
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September 2022
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Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment
ZHENLONG ZHENG, DAE SAN YOO, SHANSHAN LI, MEILING PEI, SANG GYUN LEE, JI YOUNG KIM, KEE YANG CHUNG, MI RYUNG ROH
Anticancer Research Sep 2022, 42 (9) 4359-4369; DOI: 10.21873/anticanres.15936

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Implication of IL6-positive Cancer-associated Fibroblasts in Merkel Cell Carcinoma Pathogenesis: A Possible Modulator of Immune Microenvironment
ZHENLONG ZHENG, DAE SAN YOO, SHANSHAN LI, MEILING PEI, SANG GYUN LEE, JI YOUNG KIM, KEE YANG CHUNG, MI RYUNG ROH
Anticancer Research Sep 2022, 42 (9) 4359-4369; DOI: 10.21873/anticanres.15936
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Keywords

  • Merkel cell carcinoma
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