Lung cancer patients with chronic obstructive pulmonary disease benefit from anti-PD-1/PD-L1 therapy

Abstract

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are two of the most fatal respiratory diseases, seriously threatening human health and imposing a heavy burden on families and society. Although COPD is a significant independent risk factor for LC, it is still unclear how COPD affects the prognosis of LC patients, especially when LC patients with COPD receive immunotherapy. With the development of immune checkpoint inhibition (ICI) therapy, an increasing number of inhibitors of programmed cell death-1 (PD-1) and PD-1 ligand (PD-L1) have been applied to the treatment of LC. Recent studies suggest that LC patients with COPD may benefit more from immunotherapy. In this review, we systematically summarized the outcomes of LC patients with COPD after anti-PD-1/PD-L1 treatment and discussed the tumor immune microenvironment (TIME) regulated by COPD in LC immunotherapy, which provides novel insights for the clinical treatment of LC patients with COPD.

Keywords: PD-1/PD-L1; chronic obstructive pulmonary disease (COPD); immune checkpoint inhibitors (ICIs); lung cancer (LC); tumor immune microenvironment (TIME).

Figure 1

Flowchart of the literature search for ICI therapy in LC patients with COPD.

Figure 2

Schematic presentation of the mechanisms of immune checkpoint inhibitors (ICIs) and regulation of the tumor immune microenvironment (TIME). Tumor cells bind to PD-1 on the surface of T cells by overexpressing PD-L1 or PD-L2 molecules, thus inactivating T cells for immune escape. ICIs can inhibit these interactions by binding to PD-1 or PD-L1 and then activate cytotoxic T cells and other immune cells to kill tumor cells. (A). TIL: Specific immune response to tumor cells. (B) APCs present antigens, stimulate T cells and transmit immune signals. (C) Th1: Mediates the cellular immune response and promotes cytotoxic T-cell (CTL) killing. (D) MDSCs: Inhibit the body immune cells to play normal innate and adaptive immune functions; Treg: Suppress the immune response of other cells and control self-tolerance) (by Figdraw).