Altered status of programmed death-ligand 1 after recurrence in resected lung adenocarcinoma patients

Abstract

PurposeProgrammed death-ligand 1 (PD-L1) is found to be overexpressed in non-small cell lung cancer. The present study intended to evaluate the status of PD-L1 expression in patients with resection and recurrent lung adenocarcinoma.Patients and methodsMatched resection and recurrent tumor samples were harvested from 65 lung adenocarcinoma patients. Immunohistochemistry was used to evaluate the status of PD-L1 expression. Kaplan–Meier method was used for survival analysis.ResultsA total of 65 patients of lung adenocarcinoma were enrolled. They underwent complete resection and had recurrence after adjuvant treatment. PD-L1 expression was identified in 43.1% (28/65) of resection samples vs 55.4% (36/65) of recurrent samples. Ten patients shifted from negative to positive, whereas another two samples showed the opposite. Patients with PD-L1 expression showed worse disease-free survival than the PD-L1-negative counterparts. The expression of PD-L1 in recurrent samples was a significant favorable factor for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) (11.2 vs 8.2 months, P=0.030).ConclusionThe status of PD-L1 expression may alter between resection and recurrent samples. Also, the status of PD-L1 expression after recurrence is a better prognostic factor for EGFR-TKIs.

Expression of PD-1 and PD-L1 increase in consecutive biopsies in patients with classical Hodgkin lymphoma

“…PD-1 blockade is only currently routinely used in refractory and relapsed cHL, with high treatment response rates[ 19 ], particularly in those with high expression of PD-L1 on HRS cells[ 20 , 21 ]. In other malignancies, conventional chemotherapy upregulates expression of PD-L1 on tumor cells in cases of primary head and neck cancer[ 22 ] and lung adenocarcinoma[ 15 ]. It is unknown whether conventional front-line chemotherapy and radiotherapy upregulates expression of PD-L1 on HRS cells in cHL, however our findings with a higher expression of PD-L1 in relapsed than in primary biopsies indicate such an association.…”

“…Future studies are warranted to elucidate whether it is longer disease duration, primary treatment, or altered conditions in the relapse microenvironment that upregulate the PD-1 pathway. However, based on numerous previous studies[ 15 , 16 , 23 – 25 ], PD-1 and PD-L1 are most likely upregulated due to previous treatment with chemotherapy and radiotherapy, which could have implications regarding treatment with PD-1 inhibition in cHL.…”

“…The PD-1 pathway may also become upregulated due to longer disease duration and following anti-cancer treatment in relapsed malignancies[ 13 , 14 ]. Increased proportions of PD-L1+ tumor cells in non-small cell lung cancer (NSCLC)[ 15 ], and PD-1+ lymphocytes in multiple myeloma[ 16 ] were observed at relapse compared to primary diagnosis. It is unclear to what extent the PD-1 pathway changes in cHL when primary and relapse samples are compared.…”

Membrane-Associated RING-CH 8 Functions as a Novel PD-L1 E3 Ligase to Mediate PD-L1 Degradation Induced by EGFR Inhibitors

“…Although some studies suggested that PD-L1 expression in EGFRm NSCLCs does not affect patients' response to EGFR-TKIs including osimertinib (20,21), other studies reported that high PD-L1 expression correlates with primary resistance to EGFR-TKIs (13)(14)(15) or that increased PD-L1 is associated with acquired resistance to EGFR-TKIs (10,22). Interestingly, there are also studies showing that PD-L1 expression may serve as a favorable biomarker predicting better response to EGFR-TKIs (16)(17)(18)(19). Osimertinib clearly has a direct effect on eliminating EGFRm NSCLC cells via induction of apoptosis as we previously demonstrated (30).…”

“…However, EGFR signaling positively regulates PD-L1 levels (10)(11)(12). Moreover, PD-L1 expression affects therapeutic outcomes of EGFR-TKI treatment of EGFRm NSCLCs (13)(14)(15)(16)(17)(18)(19), albeit with conflicting reports (20,21) and is even linked to acquired resistance to EGFR-TKIs (10,22).…”