bims-maitce 2024-02-18 papers

Issue of 2024–02–18
four papers selected by
Andy E. Hogan, Maynooth University

Oncoimmunology. 2024 ;13(1): 2312631

Immune checkpoint blockade improves the activation and function of circulating mucosal-associated invariant T (MAIT) cells in patients with non-small cell lung cancer.

Patrik Sundström, Nikita Dutta, William Rodin, Andreas Hallqvist, Sukanya Raghavan, Marianne Quiding Järbrink.

Mucosal-associated invariant T (MAIT) cells constitute one of the most numerous unconventional T cell subsets, and are characterized by rapid release of Th1- and Th17-associated cytokines and increased cytotoxic functions following activation. MAIT cells accumulate in tumor tissue but show an exhausted phenotype. Here, we investigated if immune checkpoint blockade (ICB) with antibodies to PD-1 or PD-L1 affects the function of circulating MAIT cells from non-small cell lung cancer patients. ICB increased the proliferation and co-expression of the activation markers HLA-DR and CD38 on MAIT cells in most patients after the first treatment cycle, irrespective of treatment outcome. Furthermore, production of cytokines, especially TNF and IL-2, also increased after treatment, as did MAIT cell polyfunctionality. These results indicate that MAIT cells respond to ICB, and that MAIT cell reinvigoration may contribute to tumor regression in patients undergoing immune checkpoint therapy.

Keywords: Immune checkpoint blockade; MAIT cell; PD-1; immunotherapy; non-small cell lung cancer

DOI: https://doi.org/10.1080/2162402X.2024.2312631

J Allergy Clin Immunol. 2024 Feb 14. pii: S0091-6749(24)00157-X. [Epub ahead of print]

The Immune System in Neurological Diseases: What Innate-like T Cells have to Say.

Season K Wyatt-Johnson, Reham Afify, Randy R Brutkiewicz.

The immune system classically consists of two lines of defense: innate and adaptive, both of which interact with one another effectively to protect us against any pathogenic threats. Importantly, there is a diverse subset of cells known as innate-like T cells that act as a bridge between the innate and adaptive immune systems and are pivotal players in eliciting inflammatory immune responses. A growing body of evidence has demonstrated the regulatory impact of these innate-like T cells in central nervous system (CNS) diseases, and that such immune cells can traffic into the brain in multiple pathological conditions, which can be typically attributed to the breakdown of the blood-brain barrier (BBB). However, until now, it has been poorly understood whether innate-like T cells have direct protective or causative properties, particularly in CNS diseases. Therefore, in this review, our attention is focused on discussing the critical roles of three unique subsets of unconventional T-cells; namely, natural killer T (NKT) cells, γδ T cells and mucosal-associated invariant T (MAIT) cells, in the context of CNS diseases, disorders and injuries and how the interplay of these immune cells modulates CNS pathology, in an attempt to gain a better understanding of their complex functions.

Keywords: CD1d; CNS diseases; MAIT cells; MR1; NKT cells; neuroimmunology; neuroinflammation; γδ T cells

DOI: https://doi.org/10.1016/j.jaci.2024.02.003

Biomark Res. 2024 Feb 12. 12(1): 23

Characterization of T-Cell receptor repertoire in immunoglobulin a nephropathy.

Szu-Ying Ho, Chih-Chin Kao, Che-Mai Chang, Yi-Chien Chou, Wei-Tzu Luo, Wan-Hsuan Chou, I-Lin Tsai, Mai-Szu Wu, Wei-Chiao Chang.

Immunoglobulin A nephropathy (IgAN) is an autoimmune disease characterized by abnormal IgA deposition in glomerulus. Current diagnosis of IgAN still depends on renal biopsy, an invasive method that might increase the risk of clinical outcomes. Therefore, we aimed to explore the characteristics of T cell repertoire in IgAN from peripheral blood samples for identifying innovative diagnostic biomarkers. Herein, we included 8 IgAN patients, 25 non-IgAN patients, and 10 healthy controls in the study. A high-throughput immune repertoire sequencing was conducted to investigate the T-cell receptor beta-chain (TCRβ) repertoire of peripheral blood. Characteristics of TCRβ repertoire were assessed for these three distinct groups. A reduced TCRβ repertoire diversity was observed in IgAN patients compared to non-IgAN and healthy individuals. A skewed distribution toward shorter TCRβ complementarity determining region (CDR3) length was found in non-IgAN relative to IgAN patients. In addition, the differences in usages of five TRBV genes (TRBV5-4, TRBV6-4, TRBV12-1, TRBV16, and TRBV21-1) were identified between IgAN, non-IgAN, and healthy subjects. Of note, the TRBV6-4 gene, which is associated with mucosal-associated invariant T (MAIT) cells, exhibited higher usage in IgAN patients, suggesting potential importance of MAIT cells in IgAN. In short, our findings supported TCR repertoire characteristics as potential biomarkers for IgAN diagnosis.

Keywords: Immunoglobulin A nephropathy (IgAN); T-cell receptor (TCR) repertoire; TCR sequencing

DOI: https://doi.org/10.1186/s40364-024-00572-2

Cytometry A. 2024 Feb 11.

OMIP-101: 27-color flow cytometry panel for immunophenotyping of major leukocyte populations in fixed whole blood.

Claire Imbratta, Timothy D Reid, Asma Toefy, Thomas J Scriba, Elisa Nemes.

This 27-color flow cytometry antibody panel allows broad immune-profiling of major leukocyte subsets in human whole blood (WB). It includes lineage markers to identify myeloid and lymphoid cell populations including granulocytes, monocytes, myeloid dendritic cells (mDCs), natural killer (NK) cells, NKT-like cells, B cells, conventional CD4 and CD8 T cells, γδ T cells, mucosa-associated invariant T (MAIT) cells and innate lymphoid cells (ILC). To further characterize each of these populations, markers defining stages of cell differentiation (CCR7, CD27, CD45RA, CD127, CD57), cytotoxic potential (perforin, granzyme B) and cell activation/proliferation (HLA-DR, CD38, Ki-67) were included. This panel was developed for quantifying absolute counts and phenotyping major leukocyte populations in cryopreserved, fixed WB collected from participants enrolled in large multi-site tuberculosis (TB) vaccine clinical trials. This antibody panel can be applied to profile major leukocyte subsets in other sample types such as fresh WB or peripheral blood mononuclear cells (PBMCs) with only minor additional optimization.

Keywords: absolute counts; clinical trials; fixed whole blood; high-dimensional flow cytometry; immune cell subsets; immunophenotyping

DOI: https://doi.org/10.1002/cyto.a.24827