AUTHOR=Sellmer Laura , Kovács Julia , Walter Julia , Kumbrink Jörg , Neumann Jens , Kauffmann-Guerrero Diego , Kiefl Rosemarie , Schneider Christian , Jung Andreas , Behr Jürgen , Tufman Amanda TITLE=Markers of Immune Cell Exhaustion as Predictor of Survival in Surgically-Treated Early-Stage NSCLC JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.858212 DOI=10.3389/fimmu.2022.858212 ISSN=1664-3224 ABSTRACT=Background

Tumor tissue as well as regional lymph nodes are removed during curative surgery for early-stage non-small cell lung cancer (NSCLC). These tissues provide a unique snapshot of the immune cell composition at the time of surgery. We investigated the immune landscape in matched tumor tissue, tumor bearing (tb) and non-tumor bearing (ntb) N1 as well as N2 lymph nodes (LNs) in patients with NSCLC and its relation to survival.

Methods

Internal hospital databases were screened for surgically treated NSCLC patients for whom tumor tissue, tbLNs as well as N1 and N2 ntbLNs were available. Clinical as well as demographic data were extracted from hospital records. Expression profiling of 770 immune-related genes was performed using the PanCancer IO 360 panel by NanoString Technologies.

Results

We identified 190 surgically treated patients of whom 16 fulfilled inclusion criteria and had sufficient archived tissue. The Tumor Immune Dysfunction and Exclusion (TIDE) score in N1 tumor-free lymph nodes was associated with OS. TIM-3 expression was inversely correlated with TIDE scores in affected LNs, N1 and N2 ntbLNs. Levels of CD8 expression were significantly higher in TIDE High compared to TIDE Low patients. TIM-3 and PD-L1 were selected for the final model for OS in multivariate regression in more than one tissue.

Conclusion

Levels of immune cell exhaustion markers may indicate a dysfunctional immune status and are associated with survival after curative surgery in NSCLC.