Lactylation-driven MVP upregulation boosts immunotherapy resistance by inhibiting PD-L1 degradation in hepatocellular carcinoma

Background
Hepatocellular carcinoma (HCC) is a prevalent malignancy and the third leading cause of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have emerged as first-line therapies for advanced HCC, substantially improving c…

Autophagy inhibition improves the efficacy of anlotinib and PD-1 inhibitors in the treatment of NSCLC

Background
Cancer-associated fibroblasts (CAFs) are major non-tumor cellular components of the tumor microenvironment (TME) and are closely related to immune suppression. The enhancement of anti-programmed cell death protein-1 (PD-1) efficacy by antia…

Real-world outcomes of patients receiving salvage therapies for immune checkpoint inhibitor-resistant Merkel cell carcinoma: a rationale for future clinical trials

Background
Merkel cell carcinoma is an aggressive skin cancer that progresses to advanced/metastatic disease in~40% of patients. First-line immune checkpoint inhibitors (ICI) that block the programmed cell death protein-1/programmed death-ligand 1 axi…

Synergy between TLR3-ligand and IFN-{alpha} in the transient sensitization of “Cold” tumors to PD-1 blockade and the induction of systemic immunity

Background
Programmed cell death protein-1 (PD-1)-blocking immune checkpoint inhibitors (ICIs) are effective against highly immunogenic “hot” tumors containing high numbers of cytotoxic T-lymphocytes (CTLs), but not against poorly immunogenic “cold” t…

mRNA-encoded mutant HPV16/18 vaccines promote specific T-cell responses and synergize with anti-PD-1 checkpoint blockade in mediating therapeutic tumor regression in mice

Background
Persistent infection with high-risk human papillomavirus (HPV) 16 and 18 is a major driver of human cancer, including head and neck and cervical cancers. Although prophylactic vaccines prevent infection, effective therapies for established …

Dual targeting OX40 and IL-2 receptor enhances antitumor activity through tumor-infiltrating Treg depletion and CD8+ T-cell proliferation

Background
The strong regulatory T cell (Treg) inhibitory activity and dysfunctional cytotoxic T lymphocytes (CTLs) represent major barriers to effective antitumor immunity, particularly in late-stage cancer. Multiple anti-OX40 (aOX40) agonistic antib…

MAIT cells promote cancer progression and regulatory T cell accumulation in bladder tumor microenvironment

Background
Mucosa-associated invariant T (MAIT) cells represent a unique population of innate-like T lymphocytes capable of detecting non-peptide antigens in the context of monomorphic antigen-presenting molecules. Due to their abundance in barrier ti…

Pancreatic cancer cells escape T/NK cell immune surveillance through the expressional separation of CD58

Background
Membrane (m) CD58 is a co-stimulatory ligand that binds to CD2, and the CD2-(m) CD58 axis participates in lymphocyte activation. In addition to mCD58, a soluble form of CD58 (sCD58) has been reported in human serum, urine, and in vitro cell…

Analysis of treatment-free survival of patients with advanced melanoma receiving nivolumab as monotherapy or in combination with relatlimab in RELATIVITY-047

Background
Treatment-free survival (TFS; time spent free of systemic anticancer therapy) is increasingly used to support traditional endpoints. TFS was previously evaluated in patients with advanced melanoma treated with nivolumab plus ipilimumab. Thi…

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