2208P - The single-cell proteomic landscape of pulmonary lymphoepithelioma-like carcinoma

Background

Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare form of non-small cell lung cancer which is frequently associated with EBV infection and displays high levels of immune cell infiltration. Immunotherapy, thus, is an attractive therapeutic strategy for the disease but the treatment response has been inconsistent, indicating a gap in our understanding of the tumor microenvironment (TME) of PLELC.

Methods

Imaging mass cytometry was used in this study to map the different cellular components and interactions in 33 PLELCs at different stages (19 early-stage, 6 medium-stage, and 8 advanced-stage).

Results

Component analysis showed differential B and Treg cell composition in the TME as cancer progresses. In spatial analyses, we discovered a convergent melting trend of immune cell distribution across different stages in the tumor and non-tumor regions (p<0.05). We also identified anti-tumor immunity markers assigned to specific cellular interactions (p<0.01). In the neighborhood analysis, we found that myeloid cells near the tumor may attenuate the ability of antigenic immune responses. Furthermore, we identified two spatial structures within the TME that could impact the infiltration of immune cells and the relapse of patients, and disease relapse in patients is associated with the level of immune cells inside the tumor region (p<0.01) and fibroblasts surrounding the tumor.

Conclusions

Our findings indicate that TME is heterogeneous and dynamic along the disease progression of PLELC such that cellular components, spatial interactions, and immune cell infiltration may play a significant role in disease recurrence. Moreover, profiling the TME may be helpful for understanding and selecting different immune treatments.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.