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Published on: January 17, 2025
Potential target antigens for immunotherapy in human pancreatic cancer
F H Schmitz-Winnenthal1, L V Galindo-Escobedo, D Rimoldi
1Department of General Surgery, University Hospital of Heidelberg, Germany.
Background:
To be effective and selective, immunotherapy ideally targets specifically tumor cells and spares normal tissues. Identification of tumor specific antigens is a prerequisite to establish an effective immunotherapy. Still very little is known about the expression of tumor-related antigens in pancreatic neoplasms. Cancer Testis antigens (CT) are antigens shared by a variety of malignant tumors, but not by normal tissues with the exception of germ cells in testis. Restricted expression in neoplastic tissues and inherent immunogenic features make CT antigens ideal for use in immunotherapy. We analyzed the expression of a selected panel of nine CT antigens that have been proven to elicit an efficient immunogenic response in other malignancies. In addition we analyzed the expression of HERV-K-MEL, an immunogenic antigen of viral origin.
Methods:
Pancreatic adenocarcinoma tumor samples (n=130) were obtained intraoperatively, control tissues (n=23) were collected from cadaveric donor and from patients with chronic pancreatitis. Tumor-associated antigen expression of MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4 and HERV-K-MEL was assessed by PCR. Sequencing of PCR products were performed to assess the expression of SSX-4 in neoplastic and normal pancreatic tissues.
Results:
Three of 10 tested antigens were expressed in over 10% of malignant pancreatic tissue samples. SSX-4 was found positive in 30% of cases, SCP-1 in 19% and HERV-K-MEL in 23% of cases. No expression of CT antigens was found in non-malignant pancreatic tissue with the exception of SSX-4 and and SSX-2.
Conclusions:
Fifty two percentage of the analyzed tissues expressed at least one CT antigen. The concomitant expression of SSX-4 in both malignant and non-malignant pancreatic tissue is a new finding which may raise concerns for immunotherapy. However, HERV-K-MEL is expressed with a relatively high prevalence and may be a candidate for specific immunotherapy in a large subgroup of pancreatic cancer patients. This study advocates the analysis of patients with regard to their immunogenic profile before the onset of antigen-specific immunotherapy.
Insights
Pancreatic cancer immunotherapy faces challenges due to unknown tumor antigen expression. HERV-K-MEL shows promise as a target for specific immunotherapy in many patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Effective cancer immunotherapy requires targeting tumor-specific antigens while sparing normal tissues.
- Cancer-Testis (CT) antigens are ideal for immunotherapy due to restricted expression in tumors.
- Limited knowledge exists on CT antigen expression in pancreatic neoplasms.
Purpose of the Study:
- To analyze the expression of nine CT antigens and HERV-K-MEL in pancreatic adenocarcinoma.
- To identify potential targets for pancreatic cancer immunotherapy.
Main Methods:
- 130 pancreatic adenocarcinoma samples and 23 control tissues were analyzed.
- Expression of MAGE-A1, MAGE-A3, MAGE-A4, MAGE-A10, LAGE-1, NY-ESO-1, SCP-1, SSX-2, SSX-4, and HERV-K-MEL was assessed using PCR.
- Sequencing was used to evaluate SSX-4 expression in neoplastic and normal tissues.
Main Results:
- Three antigens (SSX-4, SCP-1, HERV-K-MEL) were expressed in over 10% of malignant pancreatic tissues.
- SSX-4 was found in 30%, SCP-1 in 19%, and HERV-K-MEL in 23% of cases.
- SSX-4 and SSX-2 showed expression in non-malignant pancreatic tissue, unlike other CT antigens.
Conclusions:
- 52% of pancreatic tissues expressed at least one CT antigen.
- Concomitant expression of SSX-4 in malignant and non-malignant tissue is a novel finding.
- HERV-K-MEL presents a promising candidate for pancreatic cancer immunotherapy due to its prevalence.
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