P06.05 Endogenous T-cell responses to ten major cancer testis antigens are frequent in esophago-gastric adenocarcinoma and antigen-specific T cells can be expanded using CD40-activated B cells
نویسندگان
چکیده
Background Tumor-associated antigens (TAAs) and especially cancer testis (CTAs) are classical tumor-specific targets for immunotherapies. As TAAs shared between patients, strategies aiming to exploit these scalable potentially applicable across different types of cancer. Loss target other mechanisms immune escape have limited the success CTA-directed immunotherapy. CAR T cells highly effective cellular therapies renewed interest in TAAs. Especially combined targeting multiple appears promising as recently shown lymphoma. In our study, we aimed characterize CTA-expression patterns their impact on endogenous T-cell responses, abundance antigen-presentation esophago-gastric adenocarcinoma (EGA). Materials Methods 41 treatment-naïve EGA patients were included study. RNA tumor patient-matched healthy tissue was isolated used NanoString based expression analysis 26 CTAs 25 genes associated with antigen-presentation. Based CTA expression, 10 peptide pools selected co-cultured peripheral blood mononuclear (PBMCs, n=21) determine anti-tumor responses a FluoroSpot assay. assessed using immunohistochemistry (CD3, CD8) digital image analyses area invasive margin. Autologous CD40 activated B expand antigen-specific CTAs. Results revealed pronounced differences regarding CEP55 MAGEA3/6 showing strong while NY-ESO-1 or MAGEA1 only weakly expressed. 68.3% (28/41) showed ≥ 5/10 analyzed simultaneously. line frequent 75.0% response against at least one most frequently detected Survivin (65.0% 52.6% respectively), 20.0% responded TTK pools. Overall, 6/20 ≥5 We found correlation addition, high Immune-Score increased TAA expression. Finally, demonstrate feasibility TAA-specific expansion potential strategy induce enhance EGA. Conclusions Our study highlights importance The identified relevant immunomonitoring clinical trials Personalized immunotherapeutic EGA-specific even patient specific appear this challenging disease. Disclosure Information M. Thelen: None. Garcia-Marquez: J. Lehmann: D. Keller: E. Preugszat: von Bergwelt-Baildon: B. Research Grant (principal investigator, collaborator consultant pending grants well already received); Modest; Astellas, Roche, MSD. Speakers Bureau/Honoraria (speakers bureau, symposia, expert witness); BMS. F. Consultant/Advisory Board; H.A. Schlößer: Significant; Astra Zeneca.
منابع مشابه
CD40-stimulated B lymphocytes pulsed with tumor antigens are effective antigen-presenting cells that can generate specific T cells.
Although they are considered as antigen-presenting cells, the role of antigen-unspecific B lymphocytes in antigen presentation and T-lymphocyte stimulation remains controversial. In this paper, we tested the capacity of normal human peripheral activated B cells to stimulate T cells using melanoma antigens or melanoma cell lysates. B lymphocytes activated through CD40 ligation and then pulsed wi...
متن کاملTransduced CD40-Activated B Cells Cytotoxic T Cells Using Retrovirally Efficient Generation of Antigen-Specific
متن کامل
Regulatory T Cells and Myeloid-Derived Suppressor Cells in Patients with Peptic Ulcer and Gastric Cancer
Background: Regulatory T Cells (Tregs) and Myeloid-Derived Suppressor Cells (MDSCs) are two main regulatory cells modulating the immune responses in inflammation and cancer. Objective: To investigate and compare Tregs and MDSCs in peptic ulcer and gastric cancer. Methods: Patients with dyspepsia were selected and divided into three groups of non-ulcer dyspepsia (NUD, n=22), peptic ulcer disease...
متن کاملCD40-Activated B Cells Can Efficiently Prime Antigen-Specific Naïve CD8+ T Cells to Generate Effector but Not Memory T cells
BACKGROUND The identification of the signals that should be provided by antigen-presenting cells (APCs) to induce a CD8(+) T cell response in vivo is essential to improve vaccination strategies using antigen-loaded APCs. Although dendritic cells have been extensively studied, the ability of other APC types, such as B cells, to induce a CD8(+) T cell response have not been thoroughly evaluated. ...
متن کاملEngineered antigen-specific human regulatory T cells: immunosuppression of FVIII-specific T- and B-cell responses.
Expansion of human regulatory T cells (Tregs) for clinical applications offers great promise for the treatment of undesirable immune responses in autoimmunity, transplantation, allergy, and antidrug antibody responses, including inhibitor responses in hemophilia A patients. However, polyclonal Tregs are nonspecific and therefore could potentially cause global immunosuppression. To avoid this un...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal for ImmunoTherapy of Cancer
سال: 2021
ISSN: ['2051-1426']
DOI: https://doi.org/10.1136/jitc-2021-itoc8.39