三阴性乳腺癌的个体化医疗：在一名接受新辅助化疗的患者中结合新抗原疫苗接种与基因组分析

We present a case study of a TNBC patient treated with NAC combined with dendritic cells (DCs) pulsed with a personalized tumor neoantigen vaccine. Whole-exome sequencing (WES) of germline and tumor tissue, along with tumor RNA sequencing (RNA-Seq), was performed to identify potential neoantigens. Candidate neoantigens were selected for vaccine development and evaluated for immunogenicity in peripheral blood mononuclear cells (PBMCs) through IFN-γ secretion assays, flow cytometric analysis of activation markers (CD69 and CD154) on CD4+ and CD8+ T cells, and T-cell receptor (TCR) CDR3 repertoire profiling after peptide stimulation. Germline and somatic variants were analyzed to assess hereditary risk and actionable mutations, respectively.

Selected neoantigens elicited IFN-γ responses in PBMCs prior to vaccination, indicating pre-existing immunity. Post-vaccination, enhanced immunogenicity was demonstrated by increased IFN-γ secretion, upregulation of activation markers CD69 and CD154 on CD8+ and CD4+ T cells, and polyclonal expansion of TCR CDR3 clones. Notably, an immune response against a non-vaccine neoantigen was observed following immunization, suggesting possible epitope spreading; however, responses detected in pre-vaccination samples preclude attributing this effect exclusively to vaccination. Germline WES identified a splice-altering pathogenic variant in ATM (c.2250G>A, p.Lys750=), confirming hereditary cancer predisposition. Somatic mutation analysis revealed alterations in TP53 (p.Gly199Ter), NF1 (p.Phe1593SerfsTer31), and PIK3CA (p.Glu542Lys), all supported by OncoKB level-1 evidence. DISCUSSION: This case highlights the potential of integrating precision oncology for TNBC patients undergoing NAC by identifying inherited cancer risks, detecting actionable mutations, and developing personalized neoantigen-based immunotherapies. The observation of immune responses to both vaccine and non-vaccine neoantigens raises the possibility of epitope spreading, though this finding requires cautious interpretation due to pre-existing immune responses. As a single-patient case study, these results remain preliminary and must be validated in larger cohorts.