Randomized clinical efficacy and safety study of peltopepimut-S plus cemiplimab compared to cemiplimab alone in patients with recurrent/metastatic HPV16-positive head and neck cancer

Background
Peltopepimut-S is a therapeutic vaccine, which induces specific expansion of both CD4+helper and CD8+cytotoxic T-cells against human papillomavirus type 16 (HPV16) E6/E7 oncoproteins.

Patients and methods
In a randomized phase 2 trial, we …

The spontaneous neoantigen-specific CD4+ T-cell response to a growing tumor is functionally and phenotypically diverse

Background
CD4+ T cells play a critical role in the positive and negative regulation of cellular immunity through the many functional subsets they comprise. The progressive growth of immunogenic tumors which nonetheless generate mutation-specific T ce…

HLA Ligand Atlas DIA: extending the benign immunopeptidomics resource with increased sensitivity through data-independent acquisition mass spectrometry

The human leukocyte antigen (HLA)-presented peptide repertoire, termed immunopeptidome, plays a crucial role for T-cell mediated immune reactions. Previously, the human immunopeptidome of non-malignant tissues has been mapped in a large-scale study, t…

Spatial TCR clonality and clonal expansion in the in situ microenvironment of non-small cell lung cancer

Background
T-cell activation and clonal expansion are essential to effective immunotherapy responses in non-small cell lung cancer (NSCLC). The distribution of T-cell clones may offer insights into immunogenic mechanisms and imply potential prognostic…

Multiomics integration analysis identifies tumor cell-derived MIF as a therapeutic target and potentiates anti-PD-1 therapy in osteosarcoma

Background
Osteosarcoma is a highly aggressive cancer, and the efficacy of existing therapies has plateaued. Multiomics integration analysis can identify novel therapeutic targets for various cancers and therefore shows potential toward osteosarcoma t…

HPV16 E6 and E7 expressing cancer cells suppress the antitumor immune response by upregulating KLF2-mediated IL-23 expression in macrophages

Background
Human papillomavirus type 16 (HPV16) positive cancers have a tumor environment that induces antigen-presenting cells to increase IL-23 expression. Unclear is if HPV16 E6/E7 oncoproteins expressed in these cancers play a role in upregulating…

Identification of anti-TIM-3 based checkpoint inhibitor combinations with activity in immunotherapy refractory melanoma models

Background
A significant percentage of melanomas are refractory to immune checkpoint inhibitor (ICI) monotherapies and combinations. As there are currently no effective second-line therapies available for ICI-resistant patients, we sought to identify …

Autoimmune origin for immune checkpoint inhibitor-diabetes revealed by deep immune phenotyping of the pancreas

Immune checkpoint inhibitor-diabetes (CPI-D) is an acute and non-resolving immune-related adverse event (irAE) initiated primarily by disrupting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis with monoclonal antibodies. A major l…

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