2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.06E.09 Spatial Multiomics Analysis Reveals AT2 Cells Inhibit B Cells of TLS in Pre-invasive Lung Adenocarcinoma after Neoadjuvant Immunotherapy

EP.06E.09 Spatial Multiomics Analysis Reveals AT2 Cells Inhibit B Cells of TLS in Pre-invasive Lung Adenocarcinoma after Neoadjuvant Immunotherapy

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The study examines the immune dynamics in multiple primary lung cancer (MPLC) after neoadjuvant immunotherapy, a treatment not universally effective across lesions. Specifically, it focuses on how AT2 cells influence tumor-associated tertiary lymphoid structures (TLS) to modulate immune responses in pre-invasive lung adenocarcinoma at the subsolid nodule (SSN) stage.<br /><br />Through a spatial multiomics approach, the researchers analyzed different lesion responses in a patient with MPLC. They observed that TLSs in these nodules showed varied responses to neoadjuvant immunotherapy, attributed to distinct genomic and immune landscape features of each nodule. Notably, nodules with higher genomic instability and immune evasion traits correlated with poorer therapeutic outcomes.<br /><br />The study reveals that AT2 cells, present in spatial proximity to B cells in TLSs, may exert an immunosuppressive effect, particularly in non-responding nodules. This suppression is mediated through MIF ligands, which are indicated as a potential pathway for AT2 cells to inhibit B cell activity. The findings underscore the role of AT2 cells in diminishing immune responses by undermining the activity of B cells within TLS, contributing to the variability in treatment efficacy seen in different MPLC nodules.<br /><br />Conclusively, the research offers new insights into the immunosuppressive functions of AT2 cells in lung adenocarcinoma, highlighting their potential impact on the effectiveness of immunotherapeutic strategies in treating multifocal lung cancer presentations. These findings could pave the way for more targeted treatment approaches that consider the cellular interactions within tumor microenvironments.

Asset Subtitle

Wenxiang Wang

Meta Tag

Speaker Wenxiang Wang

Topic Pathology and Biomarkers

Keywords

immune dynamics

multiple primary lung cancer

neoadjuvant immunotherapy

AT2 cells

tertiary lymphoid structures

pre-invasive lung adenocarcinoma

spatial multiomics

genomic instability

immune evasion

immunosuppressive effect