CD8 tolerance

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+ T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+ T cell and constructed a risk prediction model...

The BICSTaR (BICtegravir Single Tablet Regimen) study is investigating the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (HIV) treated in routine clinical practice. BICSTaR is an ongoing, prospective, observational cohort study across 14 countries. Treatment-naïve (TN) and treatment-experienced (TE) people with HIV (≥18 years of age) are being followed for 24 months. We present an analysis of the primary endpoint (HIV-1 RNA < 50 copies/mL; missing-equals-excluded [M = E]) at month 12 in the BICSTaR Canada cohort, including secondary (CD4 count, CD4/CD8 ratio, safety/tolerability) and exploratory (persistence, treatment satisfaction) endpoints...

Biliary tract cancer (BTC) is a highly aggressive malignancy with limited second-line therapy. We conducted this phase 2 trial to evaluate the efficacy and safety of second-line nab-paclitaxel plus sintilimab in advanced BTC. Histologically confirmed advanced BTC patients with documented disease progression after first-line chemotherapy were enrolled. Subjects received nab-paclitaxel 125 mg/m2 on days 1 and 8 plus sintilimab 200 mg on day 1, administered every 3 weeks. The primary end point was the objective response rate (ORR)...

BACKGROUND: Engineered arenavirus vectors have recently been developed to leverage the body's immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8+ T cells...

PURPOSE: Simlukafusp alfa (FAP-IL2v), a tumor-targeted immunocytokine, comprising an interleukin-2 variant moiety with abolished CD25 binding fused to human immunoglobulin G1, is directed against fibroblast activation protein-α. This phase I, open-label, multicenter, dose-escalation and extension study (NCT02627274) evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of FAP-IL2v in patients with advanced/metastatic solid tumors. METHODS: Participants received FAP-IL2v intravenously once weekly...

Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment. In this study, we assessed the potential of enhancing the efficacy of immune checkpoint inhibitors by activating innate immunity with a TLR5 agonist...

Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable ( MSS ) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs...

Metabolic Dysfunction-Associated Steatotic Liver (MASL), previously named nonalcoholic fatty liver (NAFL), is a multifactorial disease in which metabolic, genetic, and environmental risk factors play a predominant role. Obesity and type 2 diabetes act as triggers of the inflammatory response, which contributes to the progression of MASL to Metabolic Dysfunction-Associated Steatohepatitis and the development of hepatocellular carcinoma. In the liver, several parenchymal, nonparenchymal, and immune cells maintain immunological homeostasis, and different regulatory pathways balance the activation of the innate and adaptative immune system...

The accumulation of senescent cells within tissues is a hallmark of the aging process. Senescent cells are also commonly present in many age-related diseases and in the cancer microenvironment. The escape of abnormal cells from immune surveillance indicates that there is some defect in the function of cytotoxic immune cells, e.g., CD8+ T cells and natural killer (NK) cells. Recent studies have revealed that the expression of programmed death-ligand 1 (PD-L1) protein is abundantly increased in senescent cells...

The hypoxic microenvironment of solid tumors severely lowers the efficacy of oxygen-dependent photodynamic therapy (PDT). The development of hypoxia-tolerant photosensitizers for PDT is an urgent requirement. In this study, we report a novel rhenium complex (Re-TTPY) to develop a "closed-loop" therapy based on PDT-induced ferroptosis and immune therapy. Due to its electron donor-acceptor (D-A) structure, Re-TTPY undergoes energy transfer and electron transfer processes under 550 nm light irradiation, and displays hypoxia-tolerant type I/II combined PDT capability, which can generate 1 O2 , O2 ·- , and ·OH simultaneously...

The balance between T helper 1 (Th1) and T helper 2 (Th2) has a critical function in determining intratumoral immune response and anti-PD-1 immunotherapy. The level of maternal embryonic leucine zipper kinase (MELK) is reported to correlate with infiltration of immune cells in cancers, but the underlying molecular mechanism is not clarified. In the present study, we aimed to elucidate the potential function of MELK in cervical cancer. We found that MELK was upregulated and played an oncogenic role in cervical cancer...

PURPOSE: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. PATIENTS AND METHODS: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A)...

INTRODUCTION: Vitiligo is a common depigmenting skin disorder. This work is performed to systematically evaluate the efficacy and safety of fire needles combined with 308 nm excimer laser therapy in treating vitiligo. METHODS: We searched the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Randomized controlled trials (RCTs) on fire needles combined with 308 nm excimer laser therapy with 308 nm excimer laser therapy alone for vitiligo were included...

We previously demonstrated the anti-tumor effectiveness of transiently TCR redirected T cells recognizing a frameshift mutation in TGFβRII. We here describe a clinical protocol using mRNA TCR modified T cells to treat a patient with progressive, treatment-resistant metastatic MSI-H colorectal cancer. Following 12 escalating doses of autologous T cells electroporated with in vitro transcribed Radium-1 TCR mRNA we assessed T cell cytotoxicity, phenotype and cytokine production. Tumor markers and growth on CT scans were evaluated and immune cell tumor infiltrate at diagnosis assessed...

OBJECTIVE: This study aims to explore the impact of immune-enhanced enteral nutrition on postoperative outcomes, focusing on inflammatory response, intestinal mucosal barrier integrity, and immune function following laparoscopic colon cancer surgery in elderly patients. METHODS: In this single-center, randomized controlled trial, ninety-six elderly patients undergoing laparoscopic resection of colon tumors were enrolled and equally divided into two groups by random allocation...

Lung cancer (LC) is the most common cause of cancer-related death worldwide and poses a severe threat to public health. Immunotherapy with checkpoint blockers has improved the outlook for advanced non-small cell lung cancer (NSCLC) therapy. For the treatment of patients with advanced NSCLC, antibodies such as anti-programmed death 1 (anti-PD1), anti-programmed death ligand 1 (anti-PD-L1), and anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) are of paramount importance. Anti-PD-1 and anti-PD-L1 monoclonal antibody therapies are used to block the PD-1/PD-L1 pathway and identify cancerous cells to the body's defenses...

BACKGROUND: Regulatory B cells (Bregs), a specialized subset of B cells that modulate immune responses and maintain immune tolerance in malignant tumors, have not been extensively investigated in the context of bladder cancer (BLCA). This study aims to elucidate the roles of Bregs and Breg-related genes in BLCA. METHODS: We assessed Breg infiltration levels in 34 pairs of BLCA and corresponding paracancerous tissues using immunohistochemical staining. We conducted transwell and wound healing assays to evaluate the impact of Bregs on the malignant phenotype of SW780 and T24 cells...

IL-2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, while others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL-2 to CD8+ T cells, which are key anti-tumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, CD8 cis-targeted IL-2 that demonstrates over 500-fold preference for CD8+ T cells over NK and Treg cells, which may contribute to toxicity and immunosuppression, respectively...

An imbalance between exaggerated autoaggressive T cell responses, primarily CD8 + T cells, and impaired tolerogenic mechanisms underlie the development of type 1 diabetes mellitus. Disease-modifying strategies, particularly immunotherapy focusing on FoxP3 + T regulatory cells (Treg), and B cells facilitating antigen presentation for T cells, show promise. Selective depletion of B cells may be achieved with an anti-CD20 monoclonal antibody (mAb). In a 2-year-long flow cytometry follow-up, involving 32 peripheral blood T and B cell markers across three trial arms (Treg + rituximab N = 12, Treg + placebo N = 13, control N = 11), we observed significant changes...

The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity of bone metastases and increase pembrolizumab (P) activity. In a randomized phase II study, we assessed the effect of R223+P compared with R223 on tumor immune infiltration, safety, and clinical outcomes in patients with mCRPC. The primary endpoint was differences in CD4+ and CD8+ T-cell infiltrate in 8-week versus baseline bone metastasis biopsies; secondary endpoints were safety, radiographic progression-free survival (rPFS), and overall survival (OS)...