These results suggested that CD96 is crucial for the pathogenesis of AS and may be a potential target in the treatment of the disease.Ĭo-inhibitory receptors (IRs) are molecules that protect host against autoimmune reactions and maintain peripheral self-tolerance, playing an essential role in maintaining immune homeostasis. Also, low expression of CD96 elevated the phosphorylation of ERK in CD4 T cells and increased the level of TNF-α, IL-23, IL-17A, IL-6, and IFN-γ in the cell culture supernatant. In addition, the expression of CD96 was altered on human primary CD4 T cells extracted from 3 healthy volunteers and cocultured with allogeneic dendritic cells (DCs). Flow cytometry demonstrated that the frequency of CD96-positive cells among CD4 T cells in AS patients was significantly reduced and that expressed on the cells was also significantly lower than the healthy controls. Real-time Quantitative PCR Detecting System (qPCR) analysis confirmed the decreased expression of CD112R and CD96 in the peripheral blood of AS patients. Bioinformatics analysis of two datasets (GSE25101 and GSE73754), including 68 AS cases and 36 healthy controls, demonstrated that “T cell receptor signaling pathway” was significantly enriched, and two IRs (CD112R and CD96) were downregulated in AS cases. This study is aimed at exploring the correlation between IRs and ankylosing spondylitis (AS). Inhibitory receptors (IRs) play an indispensable role in regulating T cell activation and expansion. In this review, we focus on immunotherapeutic targets in NSCLC tumors and discuss how NSCLC TME may influence patients' response to immunotherapy. The interactions between the tumor and the surrounding microenvironment cause tumor growth and progression to invasion, as well as drug resistance. The malignant stroma, immune cells, and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signaling pathways. TME is a complex network of cell types that form an interconnected network, promoting tumor cell initiation, growth, and dissemination. To determine the best therapeutic approach, a thorough and in‐depth investigation of tumor microenvironment (TME) heterogeneity is required, particularly in NSCLC patients treated with immunotherapy. Although immunotherapy has shown promising results, including long‐lasting and durable responses, it is only effective for a subset of patients. Non‐small cell lung cancer (NSCLC), one of the most common types of cancer in the world, has a 5‐year survival rate ~20%. (E) A predicted protein structure model of human CD112R IgV domain (55-150 aa) using human PVRL4 (Protein Data Bank accession no. The PVR signature motifs are outlined in green frames. Similar and identical residues among this group are shaded in red. (D) Multiple sequence alignment of the IgV domains of PVR-like proteins. (C) Guide tree analysis of human CD112R and the known PVR-like proteins via the Clustal W program in MacVector 6.5. The shaded boxes refer to the shared amino acids among CD112R orthologues. (B) Alignment of the extracellular domains of human and mouse CD112R protein sequences using the MacVector 6.5 program. Two tyrosines (Y233 and Y293) in the cytoplasmic domain are underlined with one within an ITIM-like motif underlined. Predicted extracellular IgV-like and transmembrane domains are highlighted in blue and red, respectively. (A) Protein sequence encoded by the human CD112R gene. The presence of two distinct CRT isoform groups, with distinct expression patterns and posttranslational modifications, supports functional specificity among plant CRTs and could account for the multiple functional roles assigned to CRTs.Characterization of human CD112R protein. Based on evolutionary relationship, a new nomenclature for plant CRTs is suggested. Furthermore, analysis of posttranslational modifications revealed differences in the glycosylation status among members within the CRT1/CRT2 isoform group. Distinct tissue-dependent expression patterns and stress-related regulation were observed for the isoform groups. The CRT3 gene appears to be most closely related to the ancestral CRT gene in higher plants. To corroborate the existence of these isoform groups, we cloned a putative CRT3 ortholog from Brassica rapa. Phylogenetic studies and expression analysis show that higher plants contain two distinct groups of CRTs: a CRT1/CRT2 group and a CRT3 group. Here, we present the first analysis, to our knowledge, of evolutionary diversity and expression profiling among different plant CRT isoforms. Calreticulin (CRT) is a multifunctional protein mainly localized to the endoplasmic reticulum in eukaryotic cells.
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