Immunogenomic features of radiologically distinctive nodules in multiple primary lung cancer

Objectives: To provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC).

Methods: The Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC.

Results: In MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8⁺ T cells. Single-cell gene analysis demonstrated that CD8⁺ T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8⁺ T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR).

Conclusions: Our findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC.