Abstract 705P
Background
Although previous studies have shown a significant association between DNA damage response (DDR) gene mutations and the efficacy of radiotherapy and immunotherapy in lung cancer patients, there are still some controversies. So, understanding the relationship between DDR gene mutations and the immune microenvironment is essential for developing therapeutic strategies. However, there is with limited research on immune cell infiltration and spatial localization.
Methods
Tumor tissue samples from 116 Chinese lung cancer patients were analyzed using next generation sequencing (NGS) and multiplex immunohistochemistry (mIHC). The mIHC were stained using the Detection Kit (Akoya), targeting 13markers Results, showing immune cellpercentages of total cells, provided insights into cell subpopulation distributions in tumor and stroma.
Results
Out of 116 patients, 60 (51.7%) had somatic or germline DDR gene mutations (mDDR) while 56 (48.3%). Analysis of patients with mDDR revealed no significant differences in the distribution of 13 immune cell subtypes within the tumor and stromal regions. Comparing immune cell infiltration between the mDDR and wDDR groups, only CD8+PD-1+ T cells (P=0.009) in the tumor stroma were significantly lower in the mDDR group. Further analysis of different sub-pathways within the DDR pathway showed that patients with HRR-MMR/BER co-mutations had significantly higher numbers of NK cells in both the tumor parenchyma (P=0.017) and stroma (P=0.011) compared to those without HRR-MMR/BER mutations. And results were seen with CD4+ T cells in the tumor parenchyma (P=0.007). Interestingly, patients with HRR-MMR/BER mutations showed no significant difference in B cell infiltration between tumor stroma and parenchyma, while patients without it had significantly fewer B cells in the parenchyma than in the stroma (P<0.001).
Conclusions
The study results indicate that DDR pathway gene mutations associated with immune microenvironment. Specifically, patients with co-mutations in HRR and MMR/BER pathways show more favorable immune features, suggesting that these sub-pathway mutations may enhance responsiveness to tumors treatment. These findings provide a foundation for optimizing precision treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
X. Hu: Financial Interests, Personal and Institutional, Non financial benefits: 3D Medicines, Inc. All other authors have declared no conflicts of interest.