Depletion of tumor-derived CXCL5 improves T cell infiltration and anti-PD-1 therapy response in an obese model of pancreatic cancer

Background
CXCR1/2 inhibitors are being implemented with immunotherapies in PDAC clinical trials. CXC-ligands are a family of cytokines responsible for stimulating these receptors; while typically secreted by activated immune cells, fibroblasts, and e…

Progesterone receptor-dependent downregulation of MHC class I promotes tumor immune evasion and growth in breast cancer

Background
Breast cancer (BC) continues to be a major health concern with 250,000 new cases diagnosed annually in the USA, 75% of which are hormone receptor positive (HR+), expressing estrogen receptor alpha (ER) and/or the progesterone receptor (PR)….

Protein arginine methyltransferase 6 enhances immune checkpoint blockade efficacy via the STING pathway in MMR-proficient colorectal cancer

Background
The emergence of immunotherapy has revolutionized the paradigm of cancer treatment with immune checkpoint blockades (ICB) in solid cancers, including colorectal cancer (CRC). However, only a small subset of CRC patients harboring deficient …

Novel anti-CD73-IL-2v bispecific fusion protein augments antitumor immunity by alleviating immunosuppressive adenosine pathways in CD8+ T cells

Background
Adenosine accumulated in the tumor microenvironment functions as an immune-modulating factor, exerting immunosuppressive actions via adenosine A2A/A2B receptor (A2AR/A2BR) in various immune cell types. CD73, a key enzymatic regulator respon…

Fc-mediated immune stimulating, pro-inflammatory and antitumor effects of anti-HER2 IgE against HER2-expressing and trastuzumab-resistant tumors

Background
Anti-human epidermal growth factor receptor 2 (HER2) IgG1-based antibody therapies significantly improve cancer prognosis, yet intrinsic or acquired resistance to fragment antigen-binding (Fab)-mediated direct effects commonly occurs. Most …

Immunosuppressive microenvironment of liver restrains chemotherapeutic efficacy in triple-negative breast cancer

Background
Patients with liver metastases of triple-negative breast cancer (TNBC) show poor prognosis compared with other metastases. Chemotherapy is the primary treatment for advanced TNBC. Tumor cell diversity and the tumor microenvironment could af…

Enhanced thrombopoiesis supplies PD-L1 to circulating immune cells via the generation of PD-L1-expressing platelets in patients with lung cancer

Background
The increased expression of programmed cell death ligand 1 (PD-L1) on a subset of immune cells in the peripheral blood has been frequently observed in patients with cancer, suggesting a relationship with PD-L1 expression in tumor tissues. I…

Targeting pyroptosis reverses KIAA1199-mediated immunotherapy resistance in colorectal cancer

Background
Despite advancements in treatment modalities, several patients with colorectal cancer (CRC) remain unresponsive to immune checkpoint inhibitor therapy. Pyroptosis, an inflammatory programmed cell death process, holds substantial promise for…

Targeted delivery of CCL3 reprograms macrophage antigen presentation and enhances the efficacy of immune checkpoint blockade therapy in hepatocellular carcinoma

Background
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide, especially in advanced stages where limited treatment options result in poor prognosis. The immunosuppressive tumor immune microenvironment (TIME), c…

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