1253P - Clinical relevance of immune factors beyond CD8+T cells and mutation status of EGFR and ALK in patients with non-small cell lung cancer

Background

EGFR-mutated or ALK-rearranged non-small cell lung cancer (NSCLC) showed poor response to therapy with immune checkpoint inhibitors (ICI), with infiltration of CD8+T cells and PD-L1 expression considered as an explanation. However, even for patients selected by PD-L1 or CD8⁺ T cells, the clinical benefit is also limited suggesting that there are additional factors to be taken into account. We evaluated immune status of the tumour microenvironment to understand better the different response to ICI therapy among patients with EGFR mutations or ALK-rearranged NSCLC.

Methods

Tumour tissue samples from NSCLC patients from June 2018 to October 2019 were collected in our hospital (n=40). Gene mutations and TMB levels were analysed by next generation sequencing (NGS), and detection of PD-L1 expression was measured using Dako PD-L1 IHC 22C3 pharmDx. CD8⁺ T cells, CD68⁺HLA-DR⁺ M1 macrophages and CD68⁺HLA-DR^- M2 macrophages, CD56^bright and CD56^dim NK cells infiltrated in tumour biopsies were detected by multiple fluorescence immunohistochemistry (mICH). Follow-up data for these patients were recorded. Statistical analysis was performed using GraphPad Prism (version 7.01) and SPSS version 21.0 (SPSS, Inc.).

Results

Lower infiltration of CD8+T cells, expression of PD-L1, and TMB levels were found in the group with EGFR mutations or ALK-rearrangements compared to wild type NSCLC (P<0.05). CD8⁺ T cells, CD56^bright NK and CD56^dim NK cells, M1 and M2 TAM, were all found both in intra-tumoral regions and tumour rim cells. Interestingly, both CD56^bright NK and CD56^dim NK cells showed lower infiltration into the tumour microenvironment in the group with EGFR mutations or ALK-rearrangements than in wild type EGFR and ALK NSCLC (P<0.05). Moreover, the ratio of NK cell infiltration, especially CD56^dim NK cells, were positively correlated with TMB level. Specifically, higher TMB levels were found in the group with infiltration of CD56^dim NK cells ≥20% compared to the group with infiltration of CD56^dim NK cells <20% (P<0.05).

Conclusions

For NSCLC patients with different EGFR and ALK status, NK cells, especially the more active population of NK cells defined as CD56dim NK cells, could be responsible for the different clinical response to ICI.

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.