Abstract

Despite numerous reports on immune checkpoint inhibitor for the treatment of non-small cell lung cancer (NSCLC), the response rate remains low but durable. Thus cisplatin still plays a major role in the treatment of NSCLC. While there are many mechanisms involved in cisplatin resistance, alteration in metabolic phenotypes with elevated levels of reactive oxygen species (ROS) are found in several cisplatin resistant tumors. These resistant cells become more reliant on mitochondria oxidative metabolism instead of glucose. Consequently, high ROS and metabolic alteration contributed to epithelial-mesenchymal transition (EMT). Importantly, recent findings indicated that EMT has a crucial role in upregulating PD-L1 expression in cancer cells. Thus, it is very likely that cisplatin resistance will lead to high expression of PD-L1/PD-1 which makes them vulnerable to anti PD-1 or anti PD-L1 antibody treatment. An understanding of the interactions between cancer cells metabolic reprogramming and immune checkpoints is critical for combining metabolism targeted therapies with immunotherapies.

Highlights

  • Treatment for early stage lung cancer is surgery but most patients already have locally advanced or metastatic disease at the time of diagnosis

  • We provide a possible link between metabolic alteration and PD-L1 expression in cisplatin resistant lung cancer (Figure 1)

  • Increased glucose metabolism in cancer cell has been recognized as the main carbon skeleton source of energy, we and others [27] have shown that cisplatin resistant (CR) cells are no longer addicted to the glycolytic pathway [11,28]

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Summary

Introduction

Treatment for early stage lung cancer is surgery but most patients already have locally advanced or metastatic disease at the time of diagnosis. Keywords Lung cancer; PD-L1; EMT; Resistance; Cisplatin A recent report on PD1 inhibitor (programmed death-1) did not show improved efficacy over standard chemotherapy as first line treatment in lung cancer and did not receive FDA approval as first line therapy for NSCLC. Despite a 50% initial response rate to platinum-based chemotherapy, the majority of lung cancer patients develop resistance to treatment.

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