Utilizing the expression profile of myeloidcells in pancreatic cancer tumor microenvironment; Towardimmunotherapy

Background: Pancreatic ductal adenocarcinoma (PDAC) is anextremely lethal pancreatic tumor because it is difficult to detectearly and does not respond well to treatments. Currently,the treatment for PDAC involves a combination of surgery andchemotherapy. Despite the improvements in therapy, PDAC remainsone of the deadliest cancers, with a ۱۰%˃ survival rateover five years. Moreover, various side effects may arise from treatments for pancreatic cancer, including digestive issues, fatigue,and neuropathy. However, it appears that immunotherapyhas the potential to improve the treatment of cancer patients.Materials and Methods: First, using the code GSE۱۵۵۶۹۸,raw single-cell sequencing data from patients with PDAC (n= ۱۶) and healthy persons (n = ۳) were downloaded from theNCBI database. Data analysis was done using the Scanpy toolbox.Data from the quality control step was initially eliminatedto remove stressed, dividing, and dead cells. The data normalizationstage was then carried out using the Scran package. TheCombat package was used to eliminate the batch effect on thesamples. Dimensional reduction was subsequently carried outusing the PCA technique. Lastly, cell clustering was performedbased on the expression of particular gene markers. The AdjustedP-value was determined by applying the Bonferroni algorithmto statistical analysis.Results: Our results showed that there is a notable increasein the number of myeloid cells. According to this finding, weexamined the expression of different genes in myeloid cellsin both healthy and cancerous conditions. The expression ofS۱۰۰A۹, as well as S۱۰۰A۴, S۱۰۰A۶, and S۱۰۰A۸, increasesin classical monocytes. Also, there is a notable increase in theexpression of S۱۰۰A۹ and S۱۰۰A۸ from the S۱۰۰ family andIFITM۲ in myeloid cells. S۱۰۰A۹ has come to light as a novelmarker for monocytic human myeloid-derived suppressor cells(MDSCs).Conclusion: According to our findings, anti-S۱۰۰A۹ and anti-S۱۰۰A۸ can be used in the treatment of PDAC. Moreover,IFITM-۲ is a BAG۳ receptor. BAG۳ activates macrophages bybinding IFITM۲. Blocking IFITM۲ may decrease the growth ofPDAC by decommissioning BAG۳.