Heterogeneity of Cancer-Associated Fibroblasts and the Tumor Immune Microenvironment in Pancreatic Cancer

Round 1

Reviewer 1 Report

The manuscript “Heterogeneity of cancer-associated fibroblasts and the tumor immune microenvironment in pancreatic cancer” by Tomohiko Shinkawa et al. is a review article which summarizes state-of-knowledge for Cancer-Associated Fibroblasts (CAFs) and their role in pancreatic cancer.

The review summarizes the possible dual role of CAFs in PDAC for which are so difficult to understand its role in PDAC progression and are difficult therapeutic target. The review contains several figures which are always helpful for easier understanding. I appreciated very much the last paragraph about clinical relevance of CAFs in pancreatic cancer, and possible design of stroma-targeting therapies.

In conclusion, I would recommend the Editor to accept the manuscript for publication in this Journal, at the present form.

Author Response

Reviewer 1: The manuscript “Heterogeneity of cancer-associated fibroblasts and the tumor immune microenvironment in pancreatic cancer” by Tomohiko Shinkawa et al. is a review article which summarizes state-of-knowledge for Cancer-Associated Fibroblasts (CAFs) and their role in pancreatic cancer.

The review summarizes the possible dual role of CAFs in PDAC for which are so difficult to understand its role in PDAC progression and are difficult therapeutic target. The review contains several figures which are always helpful for easier understanding. I appreciated very much the last paragraph about clinical relevance of CAFs in pancreatic cancer, and possible design of stroma-targeting therapies.

In conclusion, I would recommend the Editor to accept the manuscript for publication in this Journal, at the present form.

Response 1: The authors would like to thank the Reviewer for their comments.

Reviewer 2 Report

This review by Shinkawa et al. on the tumor microenvironment of Pancreatic Ductal AdenoCarcinoma (PDAC) focuses on the roles of Cancer-Associated Fibroblasts (CAF). The review is very extensive and the different newly described populations of CAF (apCAF, myCAF, iCAF) are well described. Good emphasis on single-cell RNA sequencing studies and also on the biological implications of the CAF for PDAC tumorigenesis and response/resistance to therapy. The figures are clear and helpful. I must commend the authors on a very well executed review.

Author Response

Reviewer 2: This review by Shinkawa et al. on the tumor microenvironment of Pancreatic Ductal AdenoCarcinoma (PDAC) focuses on the roles of Cancer-Associated Fibroblasts (CAF). The review is very extensive and the different newly described populations of CAF (apCAF, myCAF, iCAF) are well described. Good emphasis on single-cell RNA sequencing studies and also on the biological implications of the CAF for PDAC tumorigenesis and response/resistance to therapy. The figures are clear and helpful. I must commend the authors on a very well executed review.

Response 2: The authors would like to thank the Reviewer for their comments.