Background::
Neoantigens are newly formed antigens that have not been previously recognized
by the immune system. They may arise from altered tumor proteins that form as a result of
mutations. Although neoantigens have recently been linked to antitumor immunity in long-term survivors
of cancers, such as melanoma and colorectal cancer, their prognostic and immune-modulatory
role in many cancer types remains undefined.
Objective:
The purpose of this study is to identify prognostic markers for long-term extrahepatic
cholangiocarcinoma (EHCC) survival.
Methods:
We investigated neoantigens in EHCC, a rare, aggressive cancer with a 5-year overall
survival rate lower than 10%, using a combination of whole-exome sequencing (WES), RNA sequencing
(RNA-seq), computational biophysics, and immunohistochemistry.
Results: :
Our analysis revealed a decreased neutrophil infiltration-related trend of high-quality
neoantigen load with IC50 <500 nM (r=-0.445, P=0.043). Among 24 EHCC patients examined, we
identified four long-term survivors with WDFY3 neoantigens and none with WDFY3 neoantigens
in the short-term survivors. The WDFY3 neoantigens are associated with a lower infiltration of neutrophils
(p=0.013), lower expression of CCL5 (p=0.025), CXCL9 (p=0.036) and TIGIT (p=0.016),
and less favorable prognosis (p=0.030). In contrast, the prognosis was not significantly associated
with tumor mutation burden, neoantigen load, or immune cell infiltration.
Conclusion::
We suggest that the WDFY3 neoantigens may affect prognosis by regulating antitumor
immunity and that the WDFY3 neoantigens may be harnessed as potential targets for immunotherapy
of EHCC.
Feasibility and safety of long-term photodynamic therapy (PDT) in the palliative treatment of patients with hilar cholangiocarcinoma
