Decoding adipocyte heterogeneity through single-nucleus transcriptomics unveils subtype-specific adipocytes orchestrate immunosuppressive niches in breast cancer

Background
While adipose tissue constitutes a substantial proportion of breast composition, the functional characteristics and pathological relevance of the adipocyte microenvironment in breast carcinogenesis remain undercharacterized. This study empl…

Mutant calreticulin enables potent and selective CAR-T cell therapy in preclinical models of myeloproliferative neoplasms

Background
The adoptive transfer of T cells engineered to express chimeric antigen receptors (CAR-T) has shown high efficacy and safety in treating various hematologic malignancies. However, many hematologic disorders, such as BCR::ABL1-negative myelo…

Merkel cell carcinoma immunotherapy: key questions in the era of immune checkpoint blockade

Merkel cell carcinoma (MCC) exemplifies the paradigm of immunogenic tumors that nonetheless develop sophisticated immune evasion mechanisms. This is in line with the observation that MCC exhibits remarkable susceptibility to immune checkpoint inhibito…

Cell therapy in sarcoma: current landscape and future directions

Sarcomas are rare malignancies of mesenchymal origin, characterized by significant biological and clinical heterogeneity. Many subtypes demonstrate limited sensitivity to standard systemic treatments, including immune checkpoint inhibitors. Cell thera…

Serum cytokines predict response and survival in esophageal squamous cell carcinoma receiving chemoradiotherapy combined with anti-PD-1 antibody: analyses of two phase II clinical trials

Purpose
Chemoradiotherapy (CRT) combined with anti-PD-1 for locally advanced esophageal squamous cell carcinoma (ESCC) has shown promising efficacy but lack the predictive biomarkers to identify patients who could benefit from this therapy. The predic…

Fully human anti-B7-H4 antibody induces lysosome-dependent ferroptosis to reverse primary resistance to PD-1 blockade

Background
Although immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with certain cancers, their efficacy is largely confined to “hot” tumors characterized by robust infiltration of tumor-specific CD8+ T cells. Con…

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…

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