Oxaliplatin, ATR inhibitor and anti-PD-1 antibody combination therapy controls colon carcinoma growth, induces local and systemic changes in the immune compartment, and protects against tumor rechallenge in mice

Background
Colorectal cancer (CRC) is the third most common cancer type and one of the leading causes of cancer-related death worldwide. The treatment of advanced metastatic CRC relies on classical chemotherapy combinations (5-fluorouracil, oxaliplati…

Differential regulation of calcium-NFAT signaling pathway by Akt isoforms: unraveling effector dynamics and exhaustion of cytotoxic T lymphocytes in tumor microenvironment

Background
Impairment of Akt signaling has been observed in antigen-specific cytotoxic T lymphocytes (CTLs) during chronic viral infections or tumor progression. Despite numerous studies emphasizing Akt’s role in driving CTL effector functions, …

mTOR inhibition modulates vaccine-induced immune responses to generate memory T cells in patients with solid tumors

Background
Perturbation of the mechanistic target of rapamycin (mTOR) pathway can instruct effector versus memory cell fate of tumor antigen-specific T cells in preclinical models. In this study, we sought to understand the impact of rapamycin (siroli…

Tissue-specific properties of type 1 dendritic cells in lung cancer: implications for immunotherapy

Checkpoint inhibitors have led to remarkable benefits in non-small cell lung cancer (NSCLC), yet response rates remain below expectations. High-dimensional analysis and mechanistic experiments in clinical samples and relevant NSCLC models uncovered th…

Selective activation of interleukin-2/interleukin-15 receptor signaling in tumor microenvironment using paired bispecific antibodies

Background
Owing to their roles in promoting T cell and natural killer (NK) cell activation and proliferation, interleukins-2 (IL-2) and interleukins-15 (IL-15) have been pursued as promising pathways to target in cancer immunotherapy. Nonetheless, th…

Single-cell analysis of oncolytic virotherapy in adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATLL), an aggressive T-cell malignancy associated with human T-cell leukemia virus type 1, presents significant therapeutic challenges due to high relapse rates and resistance to therapy. Here, we present the first repo…

PLS-{alpha}-GalCer: a novel targeted glycolipid therapy for solid tumors

Background
The prototypical type I natural killer T (NKT) cell agonist, α-galactosylceramide (α-GalCer), has shown only minimal effects against solid tumors in the clinic. The most promising clinical application of α-GalCer currently…

Inhibition of stromal MAOA leading activation of WNT5A enhance prostate cancer immunotherapy by involving the transition of cancer-associated fibroblasts

Background
The interaction between stromal cells and the tumor immune microenvironment (TIME) is acknowledged as a critical driver in the progression of prostate cancer (PCa). Monoamine oxidase A (MAOA), a mitochondrial enzyme that catalyzes the degra…

A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy

Clinical trials of cancer immunotherapy (IO) were historically based on a drug development paradigm built for chemotherapies. The remarkable clinical activity of programmed cell death protein 1/programmed death ligand 1 blockade, chimeric antigen rece…

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