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

Research output: Contribution to journalArticlepeer-review


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 lowIL6+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.

Original languageEnglish
Pages (from-to)4359-4369
Number of pages11
JournalAnticancer research
Issue number9
Publication statusPublished - 2022 Sept

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2020R1A2C1102987, No. 2021R1A2C1094638), and by grants from Jilin Province Health Technology Innovation Project (No. 2017J095) and the National Natural Science Foundation of China (NSFC, No. 82060569).

Publisher Copyright:
© 2022 International Institute of Anticancer Research. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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