Comparison of mismatch repair and immune checkpoint protein profile with histopathological parameters in pancreatic, periampullary/ampullary, and choledochal adenocarcinomas

Abstract

BACKGROUND

Pancreatic, periampullary/ampullary, and choledochal adenocarcinomas are aggressive malignancies with a poor prognosis. Immune checkpoint blockade is a promising treatment option for several tumor types. H long terminal repeat-associating 2 (HHLA2), which is analogous to programmed death-ligand 1 (PD-L1), is a recently discovered member of the B7/cluster of differentiation 28 family and is expressed in many malignancies.

AIM

To analyze the expression of HHLA2 and its association with the pathologic biomarkers that predict sensitivity to immunotherapy.

METHODS

Ninety-two adenocarcinoma cases located in the pancreas, ampulla, and distal common bile duct were identified. This study assessed 106 pancreaticoduodenectomy and distal/total pancreatectomy samples that were delivered to Ankara City Hospital between 2019 and 2021. Immunohistochemistry was conducted to examine the expression of DNA mismatch repair (MMR), PD-L1, and HHLA2 proteins.

RESULTS

Patients with high HHLA2 expression had a higher mean age than those with low expression. Low HHLA2 expression was associated with high perineural invasion. HHLA2 expression was low in pathological stage T3 (pT) 3 cases and high in pathological stage T1, T2, and T4 cases. There was no correlation between HHLA2 expression and the expression of MMR proteins and PD-L1.

CONCLUSION

Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy and may serve as a novel therapeutic target for immunotherapy in advanced-stage disease.

Keywords: H long terminal repeat-associating 2; Programmed death-ligand 1; Adenocarcinoma; Pancreas; Ampulla of Vater; Distal common bile duct

Core Tip: Pancreatic, periampullary/ampullary, and choledochal adenocarcinomas are aggressive malignancies with recurrences and metastases occurring in a short period of time. Complete resection is possible in only a small proportion of patients; thus, targeted therapies are needed. H long terminal repeat-associating 2 (HHLA2), which is analogous to programmed death-ligand 1 (PD-L1), is expressed in many malignancies. Evaluation of HHLA2 expression in microsatellite stable and PD-L1-negative tumors may be useful for predicting the response of individuals to immunotherapy, and may serve as a novel therapeutic target in patients with advanced disease who do not respond to classical chemotherapy and have unresectable cancer.