Open access
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…
Innate and adaptive immune features associated with immune-related adverse events
Background
While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.
Methods
We used a mu…
Enhancing immunotherapy efficacy in NSCLC through the combined use of phenelzine and Akkermansia muciniphila to regulate gut microbial metabolite 5-HIAA
Background
Improving the efficacy of anti-programmed death 1 (PD-1) monoclonal antibody (mAb) therapy remains a major challenge for cancer immunotherapy in non-small cell lung cancer (NSCLC). Gut microbial metabolites can influence immunotherapy effic…