Extracellular granzyme K enhances PD-L1 transcription and stability via F2RL1 activation to facilitate tumor immune evasion in lung adenocarcinoma

Background
Granzyme K (GZMK) is a serine protease known for its perforin-dependent cytotoxicity. However, the non-cytotoxic role of GZMK in lung adenocarcinoma (LUAD) remains largely elusive.

Methods
Multiomics datasets were integrated to investigate…

Engineering single-vector logic-gated CAR T cells with transgene sizes beyond current limitations

Background
Engineering chimeric antigen receptor (CAR) T cells with logic-gated synthetic Notch (synNotch) receptor circuits can enhance specificity and mitigate on-target/off-tumor toxicity. However, the conventional synNotch system uses two lentivir…

ROSE12, a novel anti-CTLA-4 Fc{gamma}Rs binding-enhanced antibody activated by extracellular adenosine triphosphate, shows tumor-selective regulatory T-cell depletion and antitumor efficacy without systemic immune activation

Background
Intratumoral regulatory T cells (Tregs) are associated with diminished antitumor immunity and poor prognosis in many cancers, with tumor-infiltrating effector Tregs expressing high levels of cytotoxic T-lymphocyte-associated protein 4 (CTLA…

Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms

Adoptive cell therapy (ACT) has demonstrated curative potential in select cancers, but its translation to solid tumors such as ovarian cancer (OC) has been hindered by multiple factors, including tumor heterogeneity, immune exclusion, and a profoundly…

CD73 blockade enhances antitumor efficacy of oHSV in solid tumors by increasing macrophage-mediated antigen presentation

Background
Oncolytic herpes simplex virus (oHSV) therapy is a live virus-based immunotherapy that lyses tumor cells which release antigens and activate antitumor immunity. oHSV therapy has been shown to increase ATP production and release of extracell…

Systematic evaluation of neoepitope predictions challenges clinically observed T-cell responses and their impact on immune evasion

Abstract
Peptide presentation on human leukocyte antigens (HLAs) is essential for initiating T-cell responses and all consequences of this presentation including anticancer immunity or immune escape. Many studies have relied on in silico prediction to…

Opportunity knocking: shared tumor-associated antigen vaccines against global cancer pandemic

Shared tumor-associated antigen (TAA) vaccines are the legacy of several generations of cancer immunologists who have labored to bring them to patients with cancer to improve their disease outcome and eventually use them to prevent cancer. TAA vaccine…

Memory B cell subset shapes antitumor immunity and response to PD-1 blockade in mismatch repair-deficient colorectal cancers

Background
Mismatch repair deficiency (dMMR) colorectal cancer (CRC) is characterized by abundant tumor-infiltrating lymphocytes and tertiary lymphoid structures (TLSs). However, while B cells are pivotal for TLS formation, their function and the sign…

Tumor-infiltrating microbes and therapy response: a new frontier in triple-negative breast cancer precision oncology

Tumor-infiltrating microbes are emerging as a novel dimension of cancer biology, with growing evidence suggesting their potential as prognostic and predictive biomarkers. In this issue, Chen et al demonstrate associations between microbial signatures …

Intratumoral dendritic cell immunotherapy controls dissemination of metastasis-initiating cancer cells, even in patients with metastatic breast cancer

Patients with metastatic breast cancer (MBC) have limited opportunities for a cure, as they develop resistance to therapies and continually form new metastases. Clinical overt metastases emerge from metastasis-initiating cancer cells (MICs) that disse…

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