Identification of HLA class II-restricted T cell receptors against shared PIK3CA mutations in patients with epithelial cancers.

ABSTRACT: PIK3CA is the third most common mutated gene in epithelial cancers, behind only TP53 and KRAS. Somatic PIK3CA mutations occur predominantly in the protein's hotspot locations H1047, E545, E542 and N345, and evidence of those alterations eliciting immune responses has been limited. HLA class I-restricted TCRs against E545K and H1047L have, only recently, been identified following in vitro sensitization (IVS) with peripheral blood lymphocytes (PBL) from normal donors. In this study, we examined the immunogenicity of PIK3CA in patients with epithelial cancers of diverse histology, by testing TIL and antigen-experienced PBL against autologous hotspot PIK3CA mutations. Two distinct TCRs specific to PIK3CA^N345K, restricted by HLA-class II pair DPB1*04:01/DPA1*01:03, were identified in

SUBMITTER: Islam SMR 

PROVIDER: S-EPMC12715084 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature