Tumor-infiltrating CD8+ T cells in ALK-positive lung cancer are functionally impaired despite the absence of PD-L1 on tumor cells

Clinical studies have indicated that EGFR mutations and ALK rearrangements are associated with low response rates to blockade of the PD-1 pathway [1,2]. A correlation between EGFR mutations and low rates of concurrent PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) may cause inferior responses to PD-1 blockade [3,4]. The underlying mechanism by which ALK rearrangements lead to a low rate of responsiveness to PD-1 therapies remains unclear. Initial interest in inhibiting the PD-1 axis in ALK-driven non-small cell lung cancer (NSCLC) was sparked after preclinical studies reported that aberrant oncogenic ALK signaling drives PD-L1 expression, and that in vitro treatment with PD-1 axis inhibitors in ALK- rearranged tumor coculture with immune cells compromised tumor cell viability [5 –7].

Source: Lung Cancer - October 20, 2020 Category: Cancer & Oncology Authors: Chenxi Zeng, Yi Gao, Jing Xiong, Jiawei Lu, Jianjian Yang, Xue Wang, Yixin Cai, Lequn Li, Xiangning Fu Source Type: research