A comprehensive meta-analysis of tissue resident memory T cells and their roles in shaping immune microenvironment and patient prognosis in non-small cell lung cancer.

Tissue-resident memory T cells (T) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of T-related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique T signatures, through which we inferred the abundance of T in NSCLC.

An integrated database of experimentally validated major histocompatibility complex epitopes for antigen-specific cancer therapy.

Cancer immunotherapy represents a paradigm shift in oncology, offering a superior anti-tumor efficacy and the potential for durable remission. The success of personalized vaccines and cell therapies hinges on the identification of immunogenic epitopes capable of eliciting an effective immune response. Current limitations in the availability of immunogenic epitopes restrict the broader application of such therapies.

Tissue-resident memory T cell signatures from single-cell analysis associated with better melanoma prognosis.

Tissue-resident memory T cells (T) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of T in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the relationship between T and melanoma TIME based on multiple clinical single-cell RNA-seq datasets and developed signatures indicative of T infiltration.

Malignancy in dermatomyositis: a mono-centric retrospective study of 134 patients in China and a potential predictive model.

Objectives: To describe the demographics and phenotypes of malignancies-associated dermatomyositis (MADM) in east China and pinpoint potential factors indicative of malignancies in patients with dermatomyositis and establish a predictive model.

Methods: We retrospectively analyzed clinical data from 134 patients with adult-onset dermatomyositis hospitalized between January 2019 and May 2022 in one comprehensive hospital. Clinical data including disease course, initial symptoms and signs, and demographic information were retrieved from the Electronic Medical Records System.

Case Report: Morbihan disease treated with tofacitinib successfully.

Introduction: To date, there is no standard treatment for Morbihan disease. Several studies have reported that Morbihan disease responds well to systemic corticosteroids (prednisone and prednisolone), systemic antibiotics (tetracyclines), antihistamines (ketotifen) and surgical therapy (Lymphaticovenous anastomosis). To our knowledge, Tofacitinib, as a Janus-activated kinase (JAK) inhibitor, plays a vital role in the treatment of inflammatory and autoimmune disorders.

Potential association factors for developing effective peptide-based cancer vaccines.

Peptide-based cancer vaccines have been shown to boost immune systems to kill tumor cells in cancer patients. However, designing an effective T cell epitope peptide-based cancer vaccine still remains a challenge and is a major hurdle for the application of cancer vaccines. In this study, we constructed for the first time a library of peptide-based cancer vaccines and their clinical attributes, named CancerVaccine (https://peptidecancervaccine.

High-efficiency of genetic modification using CRISPR/Cpf1 system for engineered CAR-T cell therapy.

Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated promising efficacy in several kinds of blood cancers, including diffuse large B-cell lymphoma and acute and chronic lymphoblastic leukemia, etc. It is essential to effectively generate more potent and safer CAR-T cells through gene editing technologies for immune cell therapy. Conventional methods based on lentivirus, retrovirus and transposon, randomly integrate CAR sequence into T cell genome, which could lead to safety issues.

Influence of T Cell-Mediated Immune Surveillance on Somatic Mutation Occurrences in Melanoma.

Background: Neoantigens are presented on the cancer cell surface by peptide-restricted human leukocyte antigen (HLA) proteins and can subsequently activate cognate T cells. It has been hypothesized that the observed somatic mutations in tumors are shaped by immunosurveillance.

Methods: We investigated all somatic mutations identified in The Cancer Genome Atlas (TCGA) Skin Cutaneous Melanoma (SKCM) samples.

Single-cell transcriptome analysis of the heterogeneous effects of differential expression of tumor PD-L1 on responding TCR-T cells.

TCR-T cell therapy plays a critical role in the treatment of malignant cancers. However, it is unclear how TCR-T cells are affected by PD-L1 molecule in the tumor environment. We performed an in-depth evaluation on how differential expressions of tumor PD-L1 can affect the functionality of T cells.

The Targeting Effect of Cetuximab Combined with PD-L1 Blockade against EGFR-Expressing Tumors in a Tailored CD16-CAR T-Cell Reporter System.

The switchable chimeric antigen receptors (CARs) have shown many advantages in CAR T-cell therapy. However, human primary T-cells are required to evaluate antigen-specific adaptors by IFN-γ assay or FACS analysis, which limits the throughput of adaptor screening. A sensitive and robust CD16-CAR Jurkat NFAT-eGFP reporter system has been developed to assess the therapeutic efficacy of antibody-targeted CAR-T-cell by effectively evaluating the T-cell activation by various tumor cells and the impact of immune checkpoint inhibitor antibodies.

Selective targeting of the oncogenic G12S mutant allele by CRISPR/Cas9 induces efficient tumor regression.

: is one of the most frequently mutated oncogenes in cancers. The protein's picomolar affinity for GTP/GDP and smooth protein structure resulting in the absence of known allosteric regulatory sites makes its genomic-level activating mutations a difficult but attractive target. : Two CRISPR systems, genome-editing CRISPR/SpCas9 and transcription-regulating dCas9-KRAB, were developed to deplete the G12S mutant allele or repress its transcription, respectively, with the goal of treating -driven cancers.

Therapeutic potential of CRISPR/Cas9 gene editing in engineered T-cell therapy.

Cancer patients have been treated with various types of therapies, including conventional strategies like chemo-, radio-, and targeted therapy, as well as immunotherapy like checkpoint inhibitors, vaccine and cell therapy etc. Among the therapeutic alternatives, T-cell therapy like CAR-T (Chimeric Antigen Receptor Engineered T cell) and TCR-T (T Cell Receptor Engineered T cell), has emerged as the most promising therapeutics due to its impressive clinical efficacy. However, there are many challenges and obstacles, such as immunosuppressive tumor microenvironment, manufacturing complexity, and poor infiltration of engrafted cells, etc still, need to be overcome for further treatment with different forms of cancer.

CD47-CAR-T Cells Effectively Kill Target Cancer Cells and Block Pancreatic Tumor Growth.

CD47 is a glycoprotein of the immunoglobulin superfamily that is often overexpressed in different types of hematological and solid cancer tumors and plays important role in blocking phagocytosis, increased tumor survival, metastasis and angiogenesis. In the present report, we designed CAR (chimeric antigen receptor)-T cells that bind CD47 antigen. We used ScFv (single chain variable fragment) from mouse CD47 antibody to generate CD47-CAR-T cells for targeting different cancer cell lines.

PSSMHCpan: a novel PSSM-based software for predicting class I peptide-HLA binding affinity.

Predicting peptide binding affinity with human leukocyte antigen (HLA) is a crucial step in developing powerful antitumor vaccine for cancer immunotherapy. Currently available methods work quite well in predicting peptide binding affinity with HLA alleles such as HLA-A*0201, HLA-A*0101, and HLA-B*0702 in terms of sensitivity and specificity. However, quite a few types of HLA alleles that are present in the majority of human populations including HLA-A*0202, HLA-A*0203, HLA-A*6802, HLA-B*5101, HLA-B*5301, HLA-B*5401, and HLA-B*5701 still cannot be predicted with satisfactory accuracy using currently available methods.

IL-17A gene transfer induces bone loss and epidermal hyperplasia associated with psoriatic arthritis.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. Interleukin 17A (IL-17A) participates in many pathological immune responses; however, its role in PsA has not been fully elucidated.

IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4-CD8- entheseal resident T cells.

The spondyloarthropathies are a group of rheumatic diseases that are associated with inflammation at anatomically distal sites, particularly the tendon-bone attachments (entheses) and the aortic root. Serum concentrations of interleukin-23 (IL-23) are elevated and polymorphisms in the IL-23 receptor are associated with ankyosing spondylitis, however, it remains unclear whether IL-23 acts locally at the enthesis or distally on circulating cell populations. We show here that IL-23 is essential in enthesitis and acts on previously unidentified IL-23 receptor (IL-23R)(+), RAR-related orphan receptor γt (ROR-γt)(+)CD3(+)CD4(-)CD8(-), stem cell antigen 1 (Sca1)(+) entheseal resident T cells.

IL-23 is critical for induction of arthritis, osteoclast formation, and maintenance of bone mass.

The role of IL-23 in the development of arthritis and bone metabolism was studied using systemic IL-23 exposure in adult mice via hydrodynamic delivery of IL-23 minicircle DNA in vivo and in mice genetically deficient in IL-23. Systemic IL-23 exposure induced chronic arthritis, severe bone loss, and myelopoiesis in the bone marrow and spleen, which resulted in increased osteoclast differentiation and systemic bone loss. The effect of IL-23 was partly dependent on CD4(+) T cells, IL-17A, and TNF, but could not be reproduced by overexpression of IL-17A in vivo.

Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis.

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine secreted by a subset of memory T cells and other innate immune cells. It is associated with rheumatoid arthritis (RA) due to IL-17A expression in RA synovial fluid. The severe bone erosive rat adjuvant-induced arthritis (rAIA) and mouse collagen-induced arthritis (mCIA) models were used to address the therapeutic efficacy of anti-IL-17A treatment with a focused investigation on bone protection.

Mature B cells are critical to T-cell-mediated tumor immunity induced by an agonist anti-GITR monoclonal antibody.

An agonistic antibody DTA-1, to glucocorticoid-induced TNFR-related protein (GITR), induces T-cell activation and antitumor immunity. CD4(+) effector T cells are essential in initiating GITR-induced immune activation, and the sequentially activated cytolytic CD8(+) T cells are sufficient to induce tumor rejection. Administration of DTA-1 to a tumor-bearing mouse also induces B-cell activation illustrated by CD69 expression.

Structural, cellular, and molecular evaluation of bone erosion in experimental models of rheumatoid arthritis: assessment by μCT, histology, and serum biomarkers.

Bone erosion is a clinical endpoint for various diseases including rheumatoid arthritis. In this paper, we used rodent arthritis models with severe bone erosion to examine the structural, cellular, and molecular aspects of the inflammation-driven bone resorption process. Our data show that bone loss is observed only in chronically, severely inflamed joints.

Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction.

Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.

Introduction: The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.

Methods: Human CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-kappaB ligand (RANKL).

CD4(+) T cells from glutamic acid decarboxylase (GAD)65-specific T cell receptor transgenic mice are not diabetogenic and can delay diabetes transfer.

Glutamic acid decarboxylase (GAD)65 is an early and important antigen in both human diabetes mellitus and the nonobese diabetic (NOD) mouse. However, the exact role of GAD65-specific T cells in diabetes pathogenesis is unclear. T cell responses to GAD65 occur early in diabetes pathogenesis, yet only one GAD65-specific T cell clone of many identified can transfer diabetes.