Targeting AKR1B1 reprograms tumor-associated macrophages to enhance antitumor immunity

Background
Tumor-associated macrophages (TAMs) are key drivers of the immunosuppressive tumor microenvironment (TME), thereby limiting the efficacy of immune checkpoint inhibitors (ICIs). However, the underlying mechanisms remain unclear.

Methods
Bot…

Tumor neoantigen gene C7orf50 remodels the immune microenvironment by recruiting tumor-associated macrophages to promote hepatocellular carcinoma progression and lung metastasis

Background
Hepatocellular carcinoma (HCC) is a global health challenge with high mortality rates, particularly in patients with advanced disease and lung metastasis. T-cell receptor (TCR)-T cell therapy based on specific neoantigens, is an emerging tr…

Caninized PD-1 monoclonal antibody in oral malignant melanoma: efficacy and exploratory biomarker analysis

Background
Canine oral malignant melanoma (OMM) is a highly aggressive tumor, with several available treatment options, though few achieve durable response or complete remission. Because of its biological similarity to human mucosal melanoma, canine O…

Phase 1b/2 study of BMS-813160, a CCR2/5 dual antagonist, in combination with chemotherapy or nivolumab in patients with advanced pancreatic or colorectal cancer

Background
Cysteine–cysteine chemokine receptors 2 (CCR2) and 5 (CCR5) contribute to immune suppression in tumor microenvironments. CCR2 and CCR5 antagonists have demonstrated antitumor activity in pancreatic ductal adenocarcinoma (PDAC) and col…

Intrapatient variation in PD-L1 expression and tumor mutational burden and implications for outcomes to immune checkpoint inhibitor therapy in patients with non-small-cell lung cancer

Abstract
The recent study by Di Federico et al provides valuable insights into the intrapatient heterogeneity of programmed death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB) in non-small cell lung cancer (NSCLC), and its potential im…

CD2 costimulation bridges potent CAR-induced cytolysis and durable persistence

Background
Current second-generation CAR T cell products rely on CD28 or 4-1BB costimulatory domains, additions that respectively favor rapid cytolysis or long-term persistence, but rarely both. Preclinical modeling and retrospective analysis have lin…

Adjuvant chemo-immunotherapy shows comparable efficacy among mismatch-repair-deficient and mismatch-repair-proficient stage III colon cancer: an exploratory, reconstructed individual patient-level data analysis

The phase III ATOMIC trial recently showed that adding atezolizumab to standard adjuvant chemotherapy improved disease-free survival (DFS) in patients with mismatch-repair-deficient (dMMR) stage III colon cancer; however, its efficacy in mismatch-repa…

Oncolytic vaccinia virus encoding constitutively active EPAC remodels the tumor microenvironment to enhance therapeutic efficacy with chemotherapy and surgery

Background
Oncolytic viruses are tumor-specific immunotherapeutic agents that exploit inherent features of the tumor microenvironment to replicate, spread, and kill cancer cells. The exchange protein activated by cAMP (EPAC) is a cell signaling protei…

RIG-I agonists promote antigen-spreading and facilitate durable CAR-T responses in pancreatic ductal adenocarcinoma

Background
Pancreatic ductal adenocarcinoma (PDAC) remains largely refractory to chimeric antigen receptor (CAR)-T cell therapy. Insufficient T cell infiltration, a highly immunosuppressive microenvironment, and antigen loss pose major challenges for …

Targeting macrophage-derived SPP1 enhances CD8 T cell infiltration via ROS-DNA fragment/cGAS-STING/STAT1-mediated CXCL9/10 in tumor microenvironment

Background
Elevated levels of SPP1+ tumor-associated macrophages (TAMs) are associated with reduced CD8+ T cell infiltration and poorer prognosis in cancer patients, but direct evidence demonstrating a causal role for SPP1+ TAMs in excluding CD8+ T ce…

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