LAG-3 is expressed on TILs in tumor tissues of some patients with NSCLC. Its expression was higher in nonadenocarcinoma and correlated with PD-1/PD-L1 expression. LAG-3 positivity or both LAG-3 and PD-L1 positivity was correlated with early postoperative recurrence. LAG-3 was related to poor prognosis.
Immunotherapy has recently become widely used in lung cancer. Many oncologists are focused on cytotoxic T lymphocyte antigen‐4 (CTLA‐4), programmed cell death ligand‐1 (PD‐L1) and programmed cell death‐1 (PD‐1). Immunotherapy targeting the PD‐1/PD‐L1 checkpoints has shown promising efficacy in non‐small cell lung cancer (NSCLC), but questions remain to be answered. Among them is whether the simultaneous inhibition of other checkpoints could improve outcomes. Lymphocyte‐activation gene‐3 (LAG‐3) is another vital checkpoint that may have a synergistic interaction with PD‐1/PD‐L1. Here we review the LAG‐3 function in cancer, clinical trials with agents targeting LAG‐3 and the correlation of LAG‐3 with other checkpoints.
There has been growing interest in the use of telehealth; however, the COVID-19 pandemic and the subsequent isolation and restrictions placed on in-person services have fast-tracked implementation needs for these services. Individuals with autism spectrum disorder (ASD) have been particularly affected due to the often-intensive service needs required by this population. As a result, the aim of this review was to examine the evidence base, methodology, and outcomes of studies that have used telehealth for assessment and/or intervention with children and adolescents with ASD as well as their families over the last decade. Further, the goal is to highlight the advances in telehealth and its use with this special population. A systematic search of the literature was undertaken, with 55 studies meeting inclusion criteria and quality analysis. Specified details were extracted from each article, including participant characteristics, technology, measures, methodology/study design, and clinical and implementation outcomes. Services provided via telehealth included diagnostic assessments, preference assessments, early intervention, applied behavior analysis (ABA), functional assessment and functional communication training, and parent training. Findings, although still emerging, encouragingly suggested that services via telehealth were equivalent or better to services face-to-face. Results support the benefits to using telehealth with individuals with ASD. Future research should continue to explore the feasibility of both assessments and interventions via telehealth with those having ASD to make access to assessment services and interventions more feasible for families, while acknowledging the digital divide it could create.
Introduction
Therapeutic antibodies to immune checkpoints show promising results. Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD-L1 receptor (programmed death 1). We investigated PD-L1 protein expression and messenger RNA (mRNA) levels in SCLC.
Methods
PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28-8 PD-L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor-infiltrating immune cells (TIICs) obtained from a limited-disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive-disease SCLC was assessed for PD-L1 protein expression in tumor cells with Dako 28-8 antibody only.
Results
The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%. In the limited-disease cohort, the prevalences of PD-L1 protein expression in tumor cells with SP142 and Dako 28-8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD-L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD-L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive-disease cohort demonstrated a 14.9% positivity of PD-L1 protein expression in tumor cells with Dako 28-8 antibody.
Conclusions
A subset of SCLCs is characterized by positive PD-L1 and/or mRNA expression in tumor cells. Higher PD-L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD-L1 in SCLC is lower than that published for NSCLC. The predictive role of PD-L1 expression in SCLC treatment remains to be established.
A plasmid was constructed in which a single guanine residue was replaced with either O6-methylguanine or O6-ethylguanine, two of the DNA adducts formed by carcinogenic alkylating agents. The vectors were introduced in parallel into a pair of Chinese hamster ovary cells, in which one member of the pair was deficient in the repair enzyme O6_ alkylguanine-DNA alkyltransferase (mex-) and the other was proficient in this activity (mex'). The vectors integrated into and replicated within the respective host genomes. After intrachromosomal replication, the DNA sequence in the vicinity of the originally adducted site of each integrated vector was amplified from the host genome by using the polymerase chain reaction and was analyzed for mutations. High levels of mutation were observed from the O-methylguanine-and O6_ ethylguanine-containing vectors replicated in mex-cells (-19% for 06-methylguanine and -11% for 06-ethylguanine).
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