In the present study, we assessed the variation of PD-L1 expression of TC and IC after platinum-based neoadjuvant chemotherapy and its association with clinicopathologic characteristics and outcome in a cohort of patients with lung cancer. Our results showed that chemotherapy might play a role in upregulating PD-L1 expression on TC and IC and the elevation of PD-L1 expression on TC was associated with reduced response to chemotherapy and inferior PFS.
The prognostic role of PD-L1 expression has been extensively investigated among various cancers. Several previous studies reported that PD-L1-positive expression on TC was associated with poor prognosis in lung cancers,23–26 but few studies focused on the relationship between chemotherapy response, prognosis and the variation of PD-L1 expression after chemotherapy. The findings of Zhang et al’s27 study suggested that change of PD-L1 expression was significantly associated with chemotherapy response, and the upregulation of PD-L1 promoted a resistance response in lung cancer cells. In line with this prior study, the results of our study confirmed that the elevation of PD-L1 expression on TC was linked to inferior response to neoadjuvant chemotherapy and shorter PFS. With regard to the underlying mechanism of elevated PD-L1 expression increases the chemoresistance, the results of a previous research28 indicated that the biological interaction between PD-L1 and chemoresistance occurred through the microRNA regulatory cascade. MicroRNA-197 is downregulated in lung cancer tissues in patients resistant to platinum-based chemotherapy and the downregulation of microRNA-197 enhances PD-L1 expression. MicroRNA-197 regulates lung cancer drug resistance and tumor progression by directly targeting the cyclin-dependent kinase CKS1B as well as by indirectly targeting the transcription factor STAT3. PD-L1 expression on ICs has been strongly correlated with the density of CD4 or CD8+ tumor-infiltrating lymphocytes.29 High expression of PD-L1 on ICs may predict effective host immune responses in the presence of a favorable immune microenvironment infiltrated with increased CD4 and CD8+ T cells, which may restrain tumor growth.30 In our study, although 65.1% of patients showed elevation in the expression of PD-L1 on IC after neoadjuvant chemotherapy, no significant association was found between PD-L1 expression changes on IC and outcomes. Relatively small samples may contribute to this result and further studies are still needed to investigate the association between PD-L1 expression changes on IC and outcomes as well as its underlying mechanisms.
The current study had several limitations. First, it was a retrospective, single institutional study and the sample size was relatively small. Second, only one PD-L1 antibody, 22C3, was used in this study. Third, the PD-L1 positivity in the surgical specimens was higher than that in the biopsy specimens after chemotherapy, and the difference in specimens might be a confounding factor when comparing PD-L1 expression prechemotherapy and postchemotherapy. Hence, future prospective studies are needed to validate our results. Notwithstanding the limitations as shown above, this study provided evidence of elevated PD-L1 expression after chemotherapy and underline the necessity of tumor tissue rebiopsy and PD-L1 expression reassessment after treatment.
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