scRNA-seq reveals chemotherapy-induced tumor microenvironment changes in pancreatic ductal adenocarcinoma.

BACKGROUND

Challenges have arisen in finding an effective treatment for pancreatic ductal adenocarcinoma (PDAC). Poor outcomes have fueled ongoing efforts to exploit the tumor microenvironment (TME) in the treatment of PDAC; however, to date, treatment strategies have largely failed. Thus, a comprehensive and deep understanding of the PDAC TME is necessary. The purpose of the present study was to investigate chemotherapy-induced tumor microenvironment changes and to optimize the response to immunotherapy in PDAC.

METHODS

We analyzed publicly available single-cell RNA sequencing (scRNA-seq) PDAC (with or without standard chemotherapy) data and performed systematic analyses to elucidate novel mechanisms and to determinate the marker expression alteration induced by the chemotherapy.

RESULTS

Lysozyme (), which is usually used as a myeloid marker, was significantly increased in the tumor cells, including myeloid cells responding to chemotherapy. Additionally, chemotherapy altered the mechanism of antigen presentation and modulated the TME, which may lead to tumor drug resistance and recurrence. Chemotherapy also affected the receptor of polio virus receptor () signaling, which shifted from in T cells to in myeloid cells. Thus, (rather than ) should be the target for treatment.

CONCLUSIONS

We described the characteristics of widely expressed markers in different cell types in PDAC. Chemotherapy disrupted the TME balance, altered tumor antigen presentation, and changed signaling. Combining the appropriate chemical and immune therapies could improve the immune therapy response in PDAC.