63P - Single-cell RNA-seq combined with bulk RNA-seq revealed the involvement of pancreatic cancer tissue-resident macrophages in tumour progression and the immunotherapy response

Background

Pancreatic cancer is highly malignant and has a low cure rate. Traditional treatments are limited, and the potential of immunotherapy remains unrealized due to immune cell heterogeneity in the tumour microenvironment. Tumour-associated macrophages (TAMs), especially tissue-resident macrophages (TRMs), play complex roles in tumours.

Methods

We used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk-seq) data from pancreatic cancer patients in the GEO and TCGA databases. We analyzed macrophage heterogeneity and their functions in the tumour microenvironment. Using cell communication analysis and immune marker grading, we calculated a TAM score and analyzed survival prognosis, identifying macrophage subpopulations and their roles in tumour progression and immune response.

Results

We characterized the tumour microenvironment using scRNA-seq data and identified the TRM subpopulation. Cell communication analysis revealed interactions, including the CXCL/MIF interaction, between TRMs and various cell populations. TAM score calculations showed that TAM clusters 4, 5, 9, and 10 were significantly associated with survival risk. Predictive analyses for 5-year and 10-year mortality found that TRM cluster 4 had the highest predictive efficacy. Clinical feature analysis of patients with high and low TRM_C4 risk scores revealed significant differences in survival rates, immune cell infiltration, and immune checkpoint expression. Pre- and posttreatment TAM_C4 scores differed significantly between responders and nonresponders, with nonresponders showing increased posttreatment scores and responders showing decreased scores.

Conclusions

This study provides new insights into the heterogeneity of macrophages in pancreatic cancer and their roles in regulating tumour behaviour. Targeting specific macrophage subpopulations may lead to new therapeutic strategies, improving the effectiveness of immunotherapy and the outcomes for patients with pancreatic cancer.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.