JCSE01.22 Tumor Microenvironment Is Associated with Efficacy of PD-1/PD-L1 Inhibitors in Patients with Primary Pulmonary Lymphoepithelioma-Like Cancer

Abstract

Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is Epstein-Barr (EB) virus related subtype of non-small-cell lung cancer. Evidence of immunotherapy in LELC is scarce. The role of immune markers in tumor microenvironment and their relation with the efficacy of PD-1/PD-L1 inhibitors in LELC remain poorly explored. Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is Epstein-Barr (EB) virus related subtype of non-small-cell lung cancer. Evidence of immunotherapy in LELC is scarce. The role of immune markers in tumor microenvironment and their relation with the efficacy of PD-1/PD-L1 inhibitors in LELC remain poorly explored. A total of seventeen patients treated with PD-1/PD-L1 inhibitors in Guangdong Lung Cancer Institute were enrolled. We detected multiple immune markers including PD-L1, IDO1, TIM3, LAG3, CD4 and CD8 by immunohistochemistry in eleven of these patients. Dynamic changes of the checkpoint biomarkers in two patients (#10 and #11) treated with PD-1 inhibitors were analyzed. Tumors with 1% TPS (tumor proportion staining) were defined as PD-L1 positive. H-score of PD-L1, IDO1, TIM3 and LAG3 was calculated by multiplying percentage of positively stained cells and intensity score (0, absent; 1, weak; 2, moderate; 3, strong). For CD4 and CD8, the H-score equals the percentage of staining positive lymphocytes among all nucleated cells. In the 17 patients, most of them suffered from lines of chemotherapy (only two patients (2/17, 11.8%) received PD-1/PD-L1 inhibitors as the first line therapy). There are eight males and nine females. The median age was 47 years (range from 13 to 63). All of them were stage IIIB and IV. Thirteen of seventeen patients received single agent PD-1/PD-L1 inhibitor. PD-1/PD-L1 inhibitor showed an 82.4% disease control rate and 17.6% objective response rate. The median progression free survival was 7.4 months. The overall survival was not reached. Biomarkers of IDO1, LAG3, and TIM3 were not mutually exclusive with PD-L1, and could be highly expressed in responder patients to PD1/PD-L1 inhibitors. Notably, TIM3 expression was up-regulated at disease progression in two patients treated with PD-1 inhibitor. PD-1/PD-L1 inhibitors had preliminary good activity, and TIM3 up-regulation might be a mechanism of resistance to PD-1 inhibitors in advanced pulmonary LELC.