bims-maitce 2023-12-03 papers

Issue of 2023–12–03
three papers selected by
Andy E. Hogan, Maynooth University

Sci Rep. 2023 Nov 28. 13(1): 20990

Characterization of the TCRβ repertoire of peripheral MR1-restricted MAIT cells in psoriasis vulgaris patients.

Maja Jirouš Drulak, Zvonimir Grgić, Vera Plužarić, Marija Šola, Teuta Opačak-Bernardi, Barbara Viljetić, Kristina Glavaš, Maja Tolušić-Levak, Vlatka Periša, Martina Mihalj, Mario Štefanić, Stana Tokić.

Psoriasis vulgaris (PV) is an inflammatory skin disease largely driven by aberrant αβT cells. Mucosal-associated invariant T (MAIT) cells, which constitute the largest circulating innate-like αβT cell community in human adults, are characterized by a semi-invariant TCRVα7.2 receptor and MR1-restricted affinity toward microbial metabolites. Limited MAIT TCRα diversity is complemented by a more variable TCRβ repertoire, but its footprint in the MAIT repertoire of PV patients has never been tested. Here, we used bulk TCRSeq, MiXCR, VDJTools, and Immunarch pipelines to decipher and compare TCRβ clonotypes from flow-sorted, peripheral TCRVα7.2+MR1-5-OP-RU-tet+MAIT cells from 10 PV patients and 10 healthy, matched controls. The resulting TCRβ collections were highly private and individually unique, with small public clonotype content and high CDR3β amino acid length variability in both groups. The age-related increase in the 'hyperexpanded' clonotype compartment was observed in PV, but not in healthy MAIT repertoires. The TCRβ repertoires of PV patients were also marked by skewed TRBV/TRBJ pairing, and the emergence of PV-specific, public CDR3β peptide sequences closely matching the published CDR3β record from psoriatic skin. Overall, our study provides preliminary insight into the peripheral MAIT TCRβ repertoire in psoriasis and warrants further evaluation of its diagnostic and clinical significance.

DOI: https://doi.org/10.1038/s41598-023-48321-z

Int Immunopharmacol. 2023 Nov 27. pii: S1567-5769(23)01603-X. [Epub ahead of print]126 111276

Transcriptomic and genomic profiling of multiple primary colorectal cancers reveals intratumor heterogeneity and a distinct immune microenvironment.

Yang Li, Chen Li, Quan Wang, Ying-Jiang Ye, Ke-Wei Jiang.

This study reported on the intratumor genomic and immunological heterogeneity of different tumor lesions from a single patient with multiple primary colorectal cancer (MPCC). The goal of this study was to explore the molecular and microenvironment characteristics of tumor lesions from different primary sites in a patient with MPCC. A total of three tumor lesions located in the hepatic flexure of the transverse colon, sigmoid colon, and rectum were collected from a 72-year-old male patient with MPCC. All three tumor samples were examined by using whole-exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). The transcriptome data of The Cancer Genome Atlas (TCGA) colon cancer (COAD) dataset were explored to characterize the biological impacts of certain immune cells. Only three nonsynonymous mutations were shared by all of the tumor lesions, whereas a number of single nucleotide variant (SNV) and copy number variation (CNV) mutations were shared by tumor samples from the sigmoid colon and rectum. Transcriptomic analysis showed that tumor lesions derived from the transverse colon had decreased levels of RTK, ERK, and AKT pathway activity, thus suggesting lower oncogenic properties in the transverse lesion compared to the other two samples. Further immune landscape evaluation by using single-cell transcriptomic analysis displayed significant intratumor heterogeneity in MPCC. Specifically, more abundant mucosal-associated invariant T (MAIT) cell infiltration was found in transverse colon tumor lesions. Afterwards, we found that higher MAIT cell infiltration may correlate with a better prognosis of patients with colon cancer (immunohistochemical status was MSI-L/pMMR) by using a publicly available TCGA dataset.

Keywords: Immune infiltration; Mucosal-associated invariant T cells; Multiple primary colorectal cancer; Single-cell RNA sequencing; Tumor microenvironment

DOI: https://doi.org/10.1016/j.intimp.2023.111276

Front Immunol. 2023 ;14 1323486

Editorial: Therapeutic potential of innate and innate-like effector lymphocytes in autoimmune and inflammatory diseases.

Lan Wu, Fu-Dong Shi, Luc Van Kaer.

Keywords: immunotherapy; innate lymphocytes; innate lymphoid cells; innate-like lymphocytes; mucosal associated invariant T cells; natural killer T cells; natural killer cells

DOI: https://doi.org/10.3389/fimmu.2023.1323486