2023 World Conference on Lung Cancer (Posters)-EP06.02. Enrichment for PD-L1 High Tumors in AXL-Expressing Advanced Non-small Cell Lung Cancer (NSCLC)

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Researchers at Roswell Park Comprehensive Cancer Center in Buffalo, NY have conducted a study to investigate the relationship between the protein expression of AXL and PD-L1 in patients with advanced non-small cell lung cancer (NSCLC) who experienced disease progression on immune checkpoint inhibitor (ICI)-based therapies. AXL is a surface receptor kinase that is involved in cancer growth and metastasis, and upregulation of AXL is associated with resistance to targeted therapies.<br /><br />The study reviewed immunohistochemistry (IHC) results for AXL and PD-L1 from tissue samples of NSCLC patients who had disease progression after treatment with PD(L)-1 ICIs. AXL expression was determined using the tumor membrane percent score (TmPS), with positivity defined as a TmPS of 50 or higher with at least 1 intensity. PD-L1 expression was evaluated using the IHC 22C3 pharmDX methodology, with negative expression defined as a tumor proportion score (TPS) of 1% or lower, and positive expression defined as a TPS of 1% or higher. Positive PD-L1 expression was further categorized as intermediate (1-49%) or high (50%).<br /><br />The analysis included 66 patients with sufficient tissue for AXL IHC testing and known PD-L1 status. The majority of samples were taken before treatment (58%), while 14% of patients had post-chemotherapy or ICI re-biopsies for AXL testing. Of these cases, two showed a change in PD-L1 expression status despite only a 5% difference in TPS. Overall, the study found that in PD-L1 negative cases, 88% did not have detectable AXL expression. However, in PD-L1 high and intermediate cases, 54% and 33%, respectively, showed AXL expression.<br /><br />The study suggests a potential association between increased AXL protein expression and PD-L1 in NSCLC, particularly in tumors with high PD-L1 TPS. This finding may indicate a mechanism of resistance to ICIs that could be addressed by targeting AXL receptors. The researchers propose that a tissue screening strategy for AXL expression could be optimized by selecting NSCLC samples with positive PD-L1 expression, especially those with high PD-L1 TPS.

Asset Subtitle

Muhammad Awidi

Meta Tag

Speaker Muhammad Awidi

Topic Pathology & Biomarkers: Biomarkers for Immuno-oncology

Keywords

Roswell Park Comprehensive Cancer Center

protein expression

AXL

PD-L1

non-small cell lung cancer

NSCLC

disease progression

immune checkpoint inhibitor

AXL receptors

tissue screening