Alteration of PD-L1 expression and its prognostic impact after concurrent chemoradiation therapy in non-small cell lung cancer patients

Abstract

Concurrent chemoradiation therapy (CCRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD-1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CCRT on programmed cell death ligand-1 (PD-L1) expression on tumor cells is unknown. In this study, we analysed paired NSCLC specimens that had been obtained pre- and post-CCRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. A total of 45 patients with LA-NSCLC were included, among which there were sufficient pre- and post-CCRT specimens in 35 patients. Overall, the percentage of tumor cells with PD-L1 expression significantly decreased between pre- and post-CCRT specimens (P = 0.024). Sixteen, 15, and 4 patients had decreased, unchanged, or increased PD-L1 expression after CCRT, respectively. Median OS of patients with decreased, unchanged, or increased PD-L1 expression was 85.1, 92.8, and 14.6 months, respectively (P < 0.001). In conclusion, the percentage of PD-L1-positive tumor cells significantly decreased after CCRT. Alteration of PD-L1 expression after neoadjuvant CCRT was associated with prognosis in patients with LA-NSCLC. These data should be considered when developing the optimal approach of integrating PD-1 axis inhibitors with CCRT.

Functionally impaired follicular helper T cells induce regulatory B cells and CD14+ human leukocyte antigen‐DR− cell differentiation in non‐small cell lung cancer

“…Non‐small cell lung cancer is known to upregulate PD‐L1 expression, and high PD‐L1 expression is an independent predictor of poor prognosis . In the present study, we found that 32 NSCLC samples (56.1%) stained negative for PD‐L1, and 25 NSCLC samples (43.9%) stained positive for PD‐L1 (Figure A,B).…”

“…We found that high expression of PD‐L1 in tumor cells is significantly correlated with a high number of circulating Tfh cells in NSCLC patients. NSCLC patients with PD‐L1‐negative tumor cells had longer disease‐free survival, as reported in other studies . Gu‐Trantien et al 25 found that when Tfh cell infiltration in breast cancer patients was greater, the prognosis of patients was better.…”

Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens

“…Discordance in PD‐L1 expression occurred more frequently in patients who had received neoadjuvant therapy, and was associated predominantly with positive PD‐L1 assay in TURB and negative assay at matched cystectomy. The effect of neoadjuvant therapy on PD‐L1 expression might be due to immune suppressive effects of chemotherapy, which has also been observed in breast and non‐small‐cell lung cancer …”

“…The effect of neoadjuvant therapy on PD-L1 expression might be due to immune suppressive effects of chemotherapy, which has also been observed in breast and non-small-cell lung cancer. 9,10 Two recent studies investigated the concordance of different PD-L1 assays in urothelial cancer tissue microarrays, and found PD-L1 expression in 12-29% of samples. 11,12 Tretiakova et al found concordant PD-L1 assay outcome in matched primary urothelial carcinoma and lymph node metastasis in 90%.…”

Utility of PD‐L1 immunocytochemistry using body‐fluid cell blocks in patients with non‐small‐cell lung cancer

“…PD-L1 expression in tumor cells is altered by host immunity and during, for example, chemotherapy, tyrosine kinase inhibitor therapy, and immunotherapy. [14][15][16] Thus, our findings suggest that during the clinical course of lung cancer, the PD-L1 expression, including that in cytology/fluid material, is influenced by histology, genetic factors, medical treatment history, and the basal PD-L1 expression level of the tumor.…”