A Perspective on Cell Therapy and Cancer Vaccine in Biliary Tract Cancers (BTCs)

Han, Shuting; Lee, Suat Ying; Wang, Who-Whong; Tan, Yu Bin; Sim, Rachel Hui Zhen; Cheong, Rachael; Tan, Cherlyn; Hopkins, Richard A.; Connolly, John E.; Shuen, Timothy Wai Ho; Toh, Han Chong

doi:10.3390/cancers12113404

Cited by 23 publications

(12 citation statements)

References 69 publications

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“…The hot tumor (IS2) corresponded to a more complex TME. Inflammatory cytokines, such as, interleukin, tumor necrosis factor and TGF-β, play key roles in tumor progression and promotion of early metastasis (Han et al, 2020). Although IS2 exhibited increased immune cell infiltration, the survival of IS2 patients was worse than that of IS1.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma

Zhang

Wei

et al. 2022

Front. Cell Dev. Biol.

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Messenger RNA vaccines are considered to be a promising strategy in cancer immunotherapy, while their application on mesothelioma is still largely uncharacterized. This study aimed to identify potential antigens in mesothelioma for anti-mesothelioma mRNA vaccine development, and further determine the immune subtypes of mesothelioma for selection of suitable candidates from an extremely heterogeneous population. Gene expression data and corresponding clinicopathological information were obtained from the TCGA and gene expression omnibus, respectively. Then, the genetic alterations were compared and visualized using cBioPortal, and differentially expressed genes and their prognostic signatures were identified by GEPIA. The relationship between tumor-infiltrating immune cells and the expression of tumor antigens was systematically evaluated by TIMER online. Finally, the immune subtypes and immune landscape of mesothelioma were separately analyzed using consensus cluster and graph learning-based dimensional reduction. A total of five potential tumor antigens correlated with prognosis and infiltration of antigen-presenting cells, including AUNIP, FANCI, LASP1, PSMD8, and XPO5 were identified. Based on the expression of immune-related genes, patients with mesothelioma were divided into two immune subtypes (IS1 and IS2). Each subtype exhibited differential molecular, cellular and clinical properties. Patients with the IS1 subtype were characterized by an immune “cold” phenotype, displaying superior survival outcomes, whereas those with the IS2 subtype were characterized by an immune “hot” and immunosuppressive phenotype. Furthermore, immune checkpoints and immunogenic cell death modulators were differentially expressed between the IS1 and IS2 immune subtype tumors. The immunogenomic landscape of mesothelioma revealed a complex tumor immune microenvironment between individual patients. AUNIP, FANCI, LASP1, PSMD8, and XPO5 are putative antigens for the development of anti-mesothelioma mRNA vaccine and patients with the IS1 subtype may be considered for vaccination.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma

Zhang

Wei

et al. 2022

Front. Cell Dev. Biol.

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“…As in HCC cases, also in CCA vaccines development are also reported, such as the DC and peptide vaccines, however without presenting adequately favorable anti-neoplastic results [ 74 ], mainly attributed to T cell exclusion mechanism and TME-associated immunosuppression, by which TME prevent the aggregation of T cells that can induce harmful effects to tumors. T cell exclusion constitutes a difficult task to be faced for the achievement of the optimal response to immunotherapy [ 75 ].…”

Section: Immunotherapy Strategies For Ccamentioning

confidence: 99%

An Insight into the Novel Immunotherapy and Targeted Therapeutic Strategies for Hepatocellular Carcinoma and Cholangiocarcinoma

Trifylli

Koustas

Papadopoulos³

et al. 2022

Life

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Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) constitute highly malignant forms of primary liver cancers. Hepatocellular and bile duct carcinogenesis is a multiplex process, caused by various genetic and epigenetic alterations, the influence of environmental factors, as well as the implication of the gut microbiome, which was undervalued in the previous years. The molecular and immunological analysis of the above malignancies, as well as the identification of the crucial role of intestinal microbiota for hepatic and biliary pathogenesis, opened the horizon for novel therapeutic strategies, such as immunotherapy, and enhanced the overall survival of cancer patients. Some of the immunotherapy strategies that are either clinically applied or under pre-clinical studies include monoclonal antibodies, immune checkpoint blockade, cancer vaccines, as well as the utilization of oncolytic viral vectors and Chimeric antigen, receptor-engineered T (CAR-T) cell therapy. In this current review, we will shed light on the recent therapeutic modalities for the above primary liver cancers, as well as on the methods for the enhancement and optimization of anti-tumor immunity.

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“…Some of the tumor-associated antigens (TAAs) that could be potential targets for peptide vaccines in CCA are MUC1 and Wilms’ tumor protein 1 (WT1). Finally, there are ongoing studies of Tumor lysate-based DC vaccines, which demonstrated an early invitro efficacy, while MUC1-loaded DC vaccine used as adjuvant treatment after the resection of biliary tract and pancreatic malignancies did not exert anti-MUC-1 antibody responses [ 159 , 160 ].…”

Section: Immunotherapy In Cholangiocarcinomamentioning

confidence: 99%

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Koustas

Trifylli

Sarantis

et al. 2022

IJMS

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Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.

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A Perspective on Cell Therapy and Cancer Vaccine in Biliary Tract Cancers (BTCs)

Cited by 23 publications

References 69 publications

Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma

Identification of Potential Antigens for Developing mRNA Vaccine for Immunologically Cold Mesothelioma

An Insight into the Novel Immunotherapy and Targeted Therapeutic Strategies for Hepatocellular Carcinoma and Cholangiocarcinoma

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

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