Journal for ImmunoTherapy of Cancer
Neoadjuvant lenvatinib plus pembrolizumab in Merkel cell carcinoma: an investigator-initiated, open-label phase II trial
Background
Given the success of checkpoint inhibitor therapy in the advanced Merkel cell carcinoma (MCC) setting, there is interest in exploring immunotherapy as a neoadjuvant approach. We report the primary results of a neoadjuvant study of lenvatini…
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…