Macrophage expression patterns and polarizationpatterns in primary and metastatic pancreaticcancer; a single-cell RNA sequencing approach towardscancer genomics, transcriptomics and immunotherapies

Background: Pancreatic cancer (PC) is among the deadliesttypes of malignancies with a progressive course and its frequencyhas gradually risen over the years. inherited germlineor somatically acquired mutations are thought to cause PC development.PC prognosis is poor even with chemotherapy, radiation,and curative surgeries and management is challengingdue to surgical and chemotherapeutic complications and recurrenceof metastatic foci. Thus improvement in current therapiesis highly needed. Immunotherapy has gained many successesin treating different malignancies and different cell usages areargued. Macrophages are robust immune cells that can act invarious contexts as both anti- and pro-tumor cells. Because oftheir functional plasticity, there have been attempts to rearrangeand repolarize macrophages. In this study, we aim to comparemacrophages in primary PC and metastatic PC along with highlightinggenes and cell communications.Materials and Methods: Raw Single-cell data from primaryPC (n=۱۰) and Metastatic PC or MPC (n=۵) was gathered fromthe NCBI database. We leveraged the Scanpy toolkit for dataanalysis. Quality control phase data was deleted for the removalof dividing, stressed and dead cells. Scran package and Combatpackage was used for data normalization and batch effectremoval respectively. PCA algorithm was utilized for dimensional reduction and we clustered cells according to gene markers.Finally, the Bonferroni formula was used for the Adjustedp-value calculation.Results: UMAP revealed a noticeable reduction trend in M۱macrophages in MPC compared to primary PC. M۱ gene expressionswere significantly reduced in metastatic patients suchas IL-۶, CD۸۰, PIM۱, RTP۴, CD۱۶۳, and SLC۱۱A۱. macrophagereceptor with collagenous structure(MARCO) andmacrophage scavenger receptor ۱ (MSR۱) were shown to bedownregulated in MPC and polarized macrophages into M۲.Downregulation of chemokines was seen following metastasisnamely CXCL۱۶, CXCL۹, VCAM, and ICAM. STAT۶ – anM۲ marker- was increased in metastasis. Cell-cell communicationrevealed a reduced M۱-Cytotoxic CD۸ and increased M۱-M۲ communication in metastasis.Conclusion: According to our findings, various genes are upand downregulated in MPC and tend to affect macrophage polarizationand presence in Tumor microenvironment which alsoaffects cell communications. Further study is recommended.