ESPEC-SUIT: a versatile and robust platform to identify and track antigen-specific T cell receptors in patients with cancer

Background
Methods to identify and characterize antigen-reactive T cell receptors (TCRs) represent important tools to understand and exploit T cell responses in patients with cancer and beyond. Current methods are hampered by the rarity of individual …

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…

New insights into the role of IFN-{alpha}/{beta} and TLR7/8/9 in cancer immunotherapy and systemic autoimmunity

The role of type I interferon (IFN) in mediating tumor immunosurveillance, in situ vaccination, and response to other cancer immunotherapies is well established. The biologic and species-specific differences between type I IFN family members have not …

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…

Clonal hematopoiesis is associated with reduced response to atezolizumab in non-small cell lung cancer

Background
The acquisition of somatic mutations associated with the expansion of certain hematopoietic stem cells is known as clonal hematopoiesis (CH). Despite evidence of CH association with age-related pro-inflammatory diseases, little is known abo…

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 …

Germline whole-exome sequencing reveals FOXP3-related gene variants conferring urinary cancer susceptibility and associated with immune escape

Background
The heritability of urinary tract cancer (UTC) remains unexplained by known pathogenic germline variants, and the influence of germline variants on treatment response to immune checkpoint inhibition (ICI) has yet to be fully elucidated.

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