Abstract 63P
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.
Resources from the same session
205P - Advancing pre-clinical functional tests with immune-responsive Precision Cut Bladder Tumor Slices (PCTS)
Presenter: Sarah Richtmann
Session: Poster Display session
Resources:
Abstract
206P - Characterisation of tumour-infiltrating lymphocytes (TILs) in liver metastases (LM) and primary tumour (PT) of microsatellite stable (MSS) colorectal cancers
Presenter: Yi Hua Low
Session: Poster Display session
Resources:
Abstract
207P - ZEB2 inhibition relieves TAMs-mediated immunosuppression in EGFR-TKI resistant NSCLC
Presenter: Yunhuan Liu
Session: Poster Display session
Resources:
Abstract
208P - Targeting pro-tumor TAMs to improve immune checkpoint response of advanced bladder cancer
Presenter: Marine Leblond
Session: Poster Display session
Resources:
Abstract
209P - Mapping the landscape of immune cells for optimal index calculation using AI-powered image analysis of multiplexed immunohistochemistry in breast cancer patients
Presenter: Patricia Nielsen
Session: Poster Display session
Resources:
Abstract
210P - Precision immuno-oncology strategies to overcome drug resistance in non-small cell lung cancer
Presenter: Heidi Haikala
Session: Poster Display session
Resources:
Abstract
211P - Single-cell characterization of differentiation trajectories and drug resistance features in gastric cancer with peritoneal metastasis
Presenter: Haoxin Peng
Session: Poster Display session
Resources:
Abstract
212P - YAP/TEAD4/SP1-induced VISTA expression as a tumor cell-intrinsic mechanism of immunosuppression in colorectal cancer
Presenter: Zhehui Zhu
Session: Poster Display session
Resources:
Abstract
214P - DNA-damaging therapies trigger transcriptome and metabolism changes in peripheral NK cells of SCLC patients
Presenter: Caterina de Rosa
Session: Poster Display session
Resources:
Abstract
215P - Differential spatial gene expression and clinicopathologic characteristics are associated with exceptional response to immune checkpoint inhibition in recurrent/metastatic head and neck cancer
Presenter: Niki Gavrielatou
Session: Poster Display session
Resources:
Abstract