No abstract

No abstract

T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve response rates compared with monotherapy PD-1/L1 blockade in checkpoint naive nonsmall cell lung cancer with PD-L1 expression >50%. TIGIT mAbs with an effector-competent Fc can induce myeloid cell activation, and some have demonstrated effector T cell depletion, which carries a clinical liability of unknown significance. TIGIT Ab blockade translates to antitumor activity by enabling PVR signaling through CD226 (DNAM-1), which can be directly inhibited by PD-1. Furthermore, DNAM-1 is downregulated on tumor-infiltrating lymphocytes (TILs) in advanced and checkpoint inhibitionresistant cancers. Therefore, broadening clinical responses from TIGIT blockade into PD-L1 low or checkpoint inhibitionresistant tumors, may be induced by immune costimulation that operates independently from PD-1/L1 inhibition. TNFSF14 (LIGHT) was identified through genomic screens, in vitro functional analysis, and immune profiling of TILs as a TNF ligand that could provide broad immune activation. Accordingly, murine and human bifunctional fusion proteins were engineered linking the extracellular domain of TIGIT to the extracellular domain of LIGHT, yielding TIGIT-Fc-LIGHT. TIGIT competitively inhibited binding to all PVR ligands. LIGHT directly activated myeloid cells through interactions with LTbR (lymphotoxin b receptor), without the requirement for a competent Fc domain to engage Fcg receptors. LIGHT costimulated CD8 + T and NK cells through HVEM (herpes virus entry mediator A). Importantly, HVEM was more widely expressed than DNAM-1 on T memory stem cells and TILs across a range of tumor types. Taken together, the mechanisms of TIGIT-Fc-LIGHT promoted strong antitumor activity in preclinical tumor models of primary and acquired resistance to PD-1 blockade, suggesting that immune costimulation mediated by LIGHT may broaden the clinical utility of TIGIT blockade.

This study investigated the effect of visual input on L2 listening comprehension within the context of a North American intensive English program. The interaction between visual input and working memory (WM) was also investigated, with the aim of clarifying what role visual input, together with WM, plays in L2 listening tests. The study compared two groups of upperintermediate L1 Chinese and Arabic ESL students. All participants (N = 24) took a WM test and were divided into two groups to take a listening comprehension test under two treatment conditions: one with video and one with audio-only texts. Results indicated that the presence of visual input had a significant negative effect on listening comprehension, while working memory had no significant effect. Additionally, no interaction was found between WM and the presence or absence of visual input. This paper concludes by discussing further research questions and implications for L2 listening assessment.