Abstract B081: Tumor-associated antigen-specific immune profiling reveals distinct immunological responses to chemotherapy in pancreatic ductal adenocarcinoma
Silvia Brugiapaglia, Erika Ostorero, Bruno Castellino, Rosella Spadi, Francesco NovelliAbstract
Background:
Pancreatic ductal adenocarcinoma (PDAC) is characterized by profound immunosuppression and limited responsiveness to immunotherapy. We hypothesized that integrating functional antigen-specific immune responses with clinical parameters could identify patients more likely to benefit from antigen-directed immunotherapies.
Methods:
Peripheral blood mononuclear cells (PBMCs) and serum samples were collected from PDAC patients before and after treatment with Gemcitabine/nab-paclitaxel (GemNab) or FOLFIRINOX. Humoral immunity was assessed by measuring antibodies against a panel of tumor-associated antigens (TAAs). PBMCs were stimulated in vitro with the same antigen panel, and antigen-specific responses were evaluated by lymphocyte proliferation together with IFN-γ and IL-10 secretion. These immune parameters were integrated into a composite immune suitability score, which was further combined with clinically relevant variables, including overall survival, CA19-9, CEA, performance status, and metastatic burden, to define patient-specific immune profiles and evaluate their potential suitability for antigen-directed immunotherapy.
Results:
Chemotherapy differentially remodeled antigen-specific immunity. Compared with FOLFIRINOX, GemNab was associated with a more consistent enhancement of TAA-specific immune responses, characterized by increased proliferative capacity and a predominance of IFN-γ over IL-10 production. Considerable interpatient heterogeneity was observed in both humoral and cellular immune responses. Integration of immune and clinical variables generated distinct immune suitability profiles that stratified patients according to the strength of their antigen-specific immunity and clinical outcome. Patients with higher composite immune suitability scores displayed more favorable clinical characteristics and mounted stronger post-treatment antigen-specific responses, identifying a subgroup with increased immunotherapeutic potential.
Conclusions:
Integrative profiling of antigen-specific humoral and cellular immunity, combined with clinical parameters, enables the identification of distinct immune suitability profiles in PDAC. This approach provides a framework for patient stratification and reveals an immunotherapeutic window in which antigen-targeted vaccination and other antigen-specific immunotherapies may be most effective.
Citation Format:
Silvia Brugiapaglia, Erika Ostorero, Bruno Castellino, Rosella Spadi, Francesco Novelli. Tumor-associated antigen-specific immune profiling reveals distinct immunological responses to chemotherapy in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B081.