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CD73 plays a critical role in the pathogenesis and immune escape in pancreatic ductal adenocarcinoma (PDAC). AB680, an exceptionally potent and selective inhibitor of CD73, is administered in an early clinical trial, in conjunction with gemcitabine and anti‐PD‐1 therapy, for the treatment of PDAC. Nevertheless, the specific therapeutic efficacy and immunoregulation within the microenvironment of AB680 monotherapy in PDAC have yet to be fully elucidated. In this study, AB680 exhibits a significant effect in augmenting the infiltration of responsive CD8+ T cells and prolongs the survival in both subcutaneous and orthotopic murine PDAC models. In parallel, it also facilitates chemotaxis of myeloid‐derived suppressor cells (MDSCs) by tumor‐derived CXCL5 in an AMP‐dependent manner, which may potentially contribute to enhanced immunosuppression. The concurrent administration of AB680 and PD‐1 blockade, rather than gemcitabine, synergistically restrain tumor growth. Notably, gemcitabine weakened the efficacy of AB680, which is dependent on CD8+ T cells. Finally, the supplementation of a CXCR2 inhibitor is validated to further enhance the therapeutic efficacy when combined with AB680 plus PD‐1 inhibitor. These findings systematically demonstrate the efficacy and immunoregulatory mechanism of AB680, providing a novel, efficient, and promising immunotherapeutic combination strategy for PDAC. [ABSTRACT FROM AUTHOR]

Background: Intraductal papillary mucinous neoplasms (IPMNs) are the precursor lesions of pancreatic cancers, requiring active surgical intervention during cancer development. However, the current criteria for predicting malignant IPMNs remain challenging and limited. Hence, this study aimed to assess the discriminatory performance of circulating cytokines, including TNF‐α, IL‐2R, IL‐6, and IL‐8, then build a novel predictive model to improve the diagnostic accuracy. Method: A total of 131 retrospective (from March 2016 to December 2019) and 53 prospective (from March 2020 to January 2021) patients who were histologically confirmed as IPMNs were consecutively collected and analyzed. Result: The circulating levels of TNF‐α, IL‐2R, IL‐6, and IL‐8 were significantly elevated in malignant IPMNs, and were verified as independent factors for malignant IPMNs (p < 0.05). Then, a novel score, the circulating cytokine score (CCS), was calculated and demonstrated as an independent predictive indicator with a higher area under the curve (AUC) than each cytokine alone (p < 0.001). Besides the CCS, two high‐risk stigmata features, the presence of solid component (PSC), and main pancreatic duct (MPD) dilation ≥10 mm were also demonstrated as independent indicators for predicting malignant IPMNs. Finally, a novel nomogram incorporating the CCS and these two high‐risk stigmata features presented a remarkable diagnostic performance, both in the training and validation cohorts with AUCs of 0.928 and 0.873, respectively. Conclusion: The CCS can be considered a novel independent predictive indicator for malignant IPMNs. Additionally, the formulated nomogram model integrating the CCS, PSC, and MPD ≥10 mm can be a valuable and promising tool for predicting the malignant transformation of IPMNs during long‐term follow‐ups to assist in timely and accurate surgical decisions. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of the most aggressive diseases in the world due to a lack of early detection, leading to an overall 5‐year survival of only 10%. In recent years, clinical trials targeted pancreatic cancer in efforts to improve survival. These studies introduce new technologies, concepts, and evidence which have instilled new optimism for improving prognosis. This review summarizes the current status of the recent (5‐year) clinical trials and describes contemporary research on pancreatic cancer, including surgical technology, diagnostic skills, traditional chemoradiotherapy, neoadjuvant chemotherapy, immunotherapy, targeted therapy, and precision medicine. Then, the future trend and direction of clinical trials on pancreatic cancer are discussed. [ABSTRACT FROM AUTHOR]

Background: The role of CD161 expression on CD8 + T cells in tumor immunology has been explored in a few studies, and the clinical significance of CD161 + CD8 + T cells in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study seeks to clarify the prognostic value and molecular characteristics linked to CD161 + CD8 + T cell infiltration in PDAC., Methods: This study included 186 patients with confirmed PDAC histology after radical resection. CD161 + CD8 + T cell infiltration was assessed using immunofluorescence staining on tumor microarrays. Flow cytometry and single-cell RNA sequencing were used to evaluate their functional status., Results: We observed significant associations between tumor-infiltrating CD161 + CD8 + T cells and clinicopathological factors, such as tumor differentiation, perineural invasion, and serum CA19-9 levels. Patients with higher tumor-infiltrating CD161 + CD8 + T cell levels had longer overall survival (OS) and recurrence-free survival (RFS) than those with lower levels. Multivariable analysis confirmed tumor-infiltrating CD161 + CD8 + T cell as an independent prognostic indicator for both OS and RFS. Notably, a combination of tumor-infiltrating CD161 + CD8 + T cell and CA19-9 levels showed a superior power for survival prediction, and patients with low tumor-infiltrating CD161 + CD8 + T cell and high CA19-9 levels had the worst survival. Furthermore, lower tumor-infiltrating CD161 + CD8 + T cells were associated with a better response to adjuvant chemotherapy. Finally, we identified tumor-infiltrating CD161 + CD8 + T cells as a unique subtype of responsive CD8 + T cells characterized by increased levels of cytotoxic cytokines and immune checkpoint molecules., Conclusion: CD161 + CD8 + T cells exhibit elevated levels of both cytotoxic and immune-checkpoint molecules, indicating as a potential and attractive target for immunotherapy. The tumor-infiltrating CD161 + CD8 + T cell is a valuable and promising predictor for survival and therapeutic response to adjuvant chemotherapy in PDAC. Further research is warranted to validate its role in the risk stratification and optimization of therapeutic strategies., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pancreatic cancer is one of the most aggressive diseases in the world due to a lack of early detection, leading to an overall 5-year survival of only 10%. In recent years, clinical trials targeted pancreatic cancer in efforts to improve survival. These studies introduce new technologies, concepts, and evidence which have instilled new optimism for improving prognosis. This review summarizes the current status of the recent (5-year) clinical trials and describes contemporary research on pancreatic cancer, including surgical technology, diagnostic skills, traditional chemoradiotherapy, neoadjuvant chemotherapy, immunotherapy, targeted therapy, and precision medicine. Then, the future trend and direction of clinical trials on pancreatic cancer are discussed., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)