
==== Front
J Gastrointest Oncol
J Gastrointest Oncol
JGO
Journal of Gastrointestinal Oncology
2078-6891
2219-679X
AME Publishing Company

jgo-15-04-2011
10.21037/jgo-24-554
Editorial
PD-L1 expression in pancreaticobiliary adenosquamous carcinoma: a potential biomarker for immunotherapy
Mahadevia Himil https://orcid.org/0000-0002-2083-5510
1 2
Babiker Hani M. 1
1 Division of Hematology/Oncology, Mayo Clinic Florida, Jacksonville, FL, USA;
2 Department of Internal Medicine, University of Missouri-Kansas City, Kansas, MO, USA
Correspondence to: Hani M. Babiker, MD. Division of Hematology/Oncology, Mayo Clinic Florida, 4500 San Pablo Rd, Jacksonville, FL 32224, USA. Email: Babiker.hani@mayo.edu.
21 8 2024
31 8 2024
15 4 20112012
21 7 2024
10 8 2024
2024 Journal of Gastrointestinal Oncology. All rights reserved.
2024
Journal of Gastrointestinal Oncology.
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.
Keywords:

Programmed death-ligand 1 (PD-L1)
immunotherapy
pancreatobiliary cancer
adenosquamous carcinoma
==== Body
pmcDr. Ward and colleagues described a very interesting study evaluating the immunogenic tumor microenvironment in the rare pancreatic and biliary cancers, pancreaticobiliary adenosquamous carcinoma (PB-ASC), published recently in the Journal of Gastrointestinal Oncology (1). Pancreatic and biliary cancers can have different histologies including adenocarcinoma, squamous carcinoma, adenosquamous carcinoma, small cell carcinoma, acinar cell carcinoma, colloid carcinoma, and other rare histologies. Indeed, treating PB-ASC has been challenging due to its resistance to standard chemotherapy and lack of data to support combination with other therapeutic modalities, including immunotherapy. Several studies investigating immunotherapeutic drugs failed to show efficacy outside microsatellite instability-high (MSI-H) in pancreaticobiliary cancers (2). These include trials investigating the role of checkpoint inhibitors, vaccines, oncolytic viruses, peptides, cytokines, and cell therapy modalities. Reports have classified pancreatic cancer into different subtypes based on molecular signatures, including aberrantly differentiated endocrine, exocrine, pancreatic progenitor, squamous, and immunogenic. However, this has not translated to defining specific targeted treatments for each of these histologies or sub-classifications (3). Hence, understanding the cohort of patients who might benefit from immunotherapeutic intervention is quintessential in this burgeoning era of drug development. The authors present a well-described study evaluating the expression of programmed death-ligand 1 (PD-L1) in patients with PB-ASC and pancreaticobiliary adenocarcinoma (PB-AC). This approach can potentially define a specific cohort of patients who might benefit from immunotherapy treatment, specifically since squamous carcinoma historically is immune sensitive. Three subclassifications were established based on the immunogenic tumor microenvironment: immune inflamed (II), immune excluded (IE), and immune desert based on lymphocyte infiltration of the tumor, stroma or parenchyma. Their results show that PB-ASC tumors had a significantly higher PD-L1 expression frequency than PB-AC. PD-L1 expression was mainly in the squamous histology and PD-L1 frequency of expression was high irrespective of the aforementioned immune subclassifications in PB-ASC. In PB-AC, PD-L1 expression were primarily in the II and IE subtypes. The pros of this study are that it introduces a potential treatment approach for this rare and aggressive pancreaticobiliary cancer phenotype, PB-ASC, in addition to potentially identifying the cohort of patients who might benefit from this treatment, those with a high frequency of PD-L1 expression. This study introduced the notion of treating patients with PB-ASC who have high PD-L1 expression with immunotherapy drugs potentially in addition to radiation if the disease is local and vascular endothelial growth factor (VEGF)-targeted drugs, perhaps in a clinical trial setting. The cons of this study are that it is low-powered albeit understandable given the rarity of the disease as well as is retrospective and somewhat descriptive. However, in our opinion, it is well designed, clearly written, and sheds light on a potential treatment approach for an otherwise aggressive and rare cancer, PB-ASC. We congratulate the authors for this effort; this study will help shape treatment approaches for this disease.

Supplementary

The article’s supplementary files as

10.21037/jgo-24-554

Acknowledgments

Funding: None.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Provenance and Peer Review: This article was commissioned by the editorial office, Journal of Gastrointestinal Oncology. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-554/coif). The authors have no conflicts of interest to declare.
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References

1 Ward JD Fowler M Robledo-Gomez A PD-L1 expression in pancreaticobiliary adenosquamous carcinoma: a single-institution case series. J Gastrointest Oncol 2024;15 :768-79. 10.21037/jgo-24-9 38756636
2 Babiker HM Zahid U Howe CL Analyzing the efficacy and safety of immunotherapy in pancreatic ductal adenocarcinoma (PDA): A systematic review and meta-analysis. J Clin Oncol 2018;36 :512. 10.1200/JCO.2018.36.4_suppl.512 29236583
3 Ray K. Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol 2016;13 :188.
