Chengpei Zhu
Simon C. Robson
Huichuan Sun
Haitao Zhao- 1Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China
- 2Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States
- 3Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
Editorial on the Research Topic
Advances in immunotherapy and combination therapy for biliary tract cancers
Biliary tract cancers (BTC) are rare and aggressive tumors often diagnosed at advanced stages, with limited options for radical surgery and a poor prognosis. Combining gemcitabine with platinum-based drugs has been the standard treatment, but recent advancements in immunotherapy, especially immune checkpoint inhibitors (ICI), offer promising alternatives. This Research Topic explores the effectiveness of immunotherapy and combination therapies for BTC, investigates the molecular mechanisms and biomarkers for identifying suitable patients, and considers strategies for integrating immunotherapy into systemic treatment.
In this Research Topic, Grant et al. reported a case of pancreatic cancer with squamous cell differentiation achieved a complete pathologic response after receiving gemcitabine and cisplatin (GC) combined with nab-paclitaxel chemotherapy, suggesting that adding standard chemotherapy to this new regimen could be a valuable first-line option for pancreatic and cholangiocarcinoma. In addition, Taghizadeh et al. published an Australian expert consensus statement on locally advanced or metastatic cholangiocarcinoma that highlights the importance of adding durvalumab, an ICI, to chemotherapy as a first-line treatment option, while emphasizing GC chemotherapy regimens in first-line treatment. The consensus also highlights the necessity of selecting specific targeted therapies based on individual genetic mutations after failure of first-line therapy. These findings highlight the evolving landscape of BTC treatment, moving towards combined therapies and personalized medicine for optimal outcomes.
Furthermore, Zhang et al. demonstrated the potential of immunotherapy conversion for initially inoperable tumors. They report a patient with unresectable intrahepatic cholangiocarcinoma (ICC) who achieved successful surgery after 6 cycles of ICI plus gemcitabine and oxaliplatin (GEMOX), highlighting the ability of this combination to shrink tumors and make them operable. Additionally, Wang et al. presented a case of primary gallbladder carcinoma with liver metastases that achieved complete remission after ICI combined with GC chemotherapy followed by surgery. Tumor analysis revealed high programmed death-ligand 1 (PD-L1) expression, suggesting this patient may have been a good candidate for immunotherapy. Additionally, the presence of macrophages and CD4+ T cells indicates a positive immune response to the treatment. These cases further support the promising role of immunotherapy in BTC treatment, particularly when combined with other therapies like chemotherapy. They also emphasize the importance of tumor characteristics like PD-L1 expression in predicting response to immunotherapy. Immunological combination chemotherapy may be a way to overcome the treatment dilemma in advanced BTC. Chemotherapy may not only up-regulate checkpoint expression and alter immune cell infiltration, it also works by disrupting strategies used by tumors to evade immune recognition. The results of several clinical trials and real-world studies suggest that the addition of targeted therapies to immune-combination chemotherapy is a promising approach for the treatment of BTC, but is also challenged by the high incidence of adverse effects (1–4). Wang et al. reported a case of progressive ICC with poor results of first-line chemotherapy, which was treated with ICI plus tyrosine kinase inhibitor combined with radiotherapy in the second line to achieve better efficacy. It is also suggested that radiotherapy can largely alter the tumour microenvironment through appropriate radiation dose and fraction, thus achieving the effect of sensitizing immunotherapy.
Finally, over the past few years, advances in precision oncology have driven the development of immuno- and targeted therapies, changing the paradigm of cancer treatment, including BTC, from a population-based perspective to individualised treatment for each patient and tumour. On this basis, enabling translational surgery for unresectable BTC, thereby further enhancing the survival of BTC patients is also a future concern (5). Although immunotherapy offers great potential for BTC, there are still a majority of patients who still fail to respond well after treatment. How to identify biomarkers (such as cell-free DNA, intestinal flora, and urinary proteins) and their intrinsic mechanisms that predict the efficacy of immunotherapy is crucial for patient selection, stratified management, and socio-economic benefits, and will be one of the main directions for future attention and research.
Author contributions
CZ: Writing – original draft, Writing – review & editing. SR: Writing – review & editing. HS: Writing – review & editing. HZ: Writing – review & editing.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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References
1. Shi G, Huang X, Wu D, Sun H, Liang F, Ji Y, et al. Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study. Signal Transduction Targeted Ther (2023) 8:106. doi: 10.1038/s41392-023-01317-7
2. Li H. A single-arm, open-label, phase II study of tislelizumab combined with lenvatinib and Gemox regimen for conversion therapy of potentially resectable locally advanced biliary tract cancers. Ann Oncol (2022) 33:S570. doi: 10.1016/j.annonc.2022.07.093
3. Zhu C, Xue J, Wang Y, Wang S, Zhang N, Wang Y, et al. Efficacy and safety of lenvatinib combined with PD-1/PD-L1 inhibitors plus Gemox chemotherapy in advanced biliary tract cancer. Front Immunol (2023) 14:1109292. doi: 10.3389/fimmu.2023.1109292
4. Zhu C, Li H, Yang X, Wang S, Wang Y, Zhang N, et al. Efficacy, safety, and prognostic factors of PD-1 inhibitors combined with lenvatinib and Gemox chemotherapy as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter real-world study. Cancer Immunol Immunother (2023) 72:2949–60. doi: 10.1007/s00262-023-03466-8
Keywords: biliary tract cancer, immunotherapy, immune checkpoint inhibitors, systemic therapy, chemotherapy
Citation: Zhu C, Robson SC, Sun H and Zhao H (2024) Editorial: Advances in immunotherapy and combination therapy for biliary tract cancers. Front. Oncol. 13:1360649. doi: 10.3389/fonc.2023.1360649
Received: 23 December 2023; Accepted: 28 December 2023;
Published: 08 January 2024.
Edited and Reviewed by:
Liang Qiao, Westmead Institute for Medical Research, AustraliaCopyright © 2024 Zhu, Robson, Sun and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Haitao Zhao, zhaoht@pumch.cn