Advanced Immunotherapeutic Strategies and Clinical Developments in Hepatocellular Carcinoma and Gastrointestinal Cancers

Dear Colleagues,

Hepatocellular carcinoma (HCC) and other gastrointestinal (GI) tract cancers affect patients from specific races and ethnicities, and account for approximately 25% of all cancers worldwide. HCC, the most common type of primary liver cancer, is the third leading cause of cancer-related death and is associated with a poor prognosis, with a 5-year survival rate below 16%. GI tract cancers are the most prevalent malignancies with high morbidity and mortality, and their incidence is rising significantly among young adults. Similarly, gastrointestinal (GI) cancers comprise a heterogeneous group of malignancies arising throughout the GI tract and are diverse in both etiology and clinical management. Collectively, GI cancers account for approximately 25% of global cancer incidence and 33% of cancer-related mortality. Although recent advances in diagnostic approaches and therapeutic strategies have led to overall improvements in outcomes, significant challenges in the effective control and management of GI cancers persist. Moreover, due to nonspecific clinical symptoms and endoscopic findings, GI involvement by hepatocellular carcinoma (HCC) is often underdiagnosed prior to death. Consequently, the current understanding of this condition is derived primarily from case reports and a limited number of literature reviews. In recent years, HCC and GI cancers are being widely studied for the immune microenvironment, pathogenesis, metastasis, drug resistance, and immunotherapy utilizing immune checkpoint inhibitors, targeted gene therapy, and combination therapy. Cutting-edge research to introduce advanced therapeutic approaches to treat the patients suffering from these cancers is improving gradually. Although advances in surgery, locoregional therapies, and systemic treatments have improved outcomes for selected patients, the prognosis for advanced-stage disease remains poor. Increasing evidence highlights the pivotal role of the tumor immune microenvironment in tumor progression, immune escape, and therapeutic resistance across HCC and GI malignancies. Over the past decade, immunotherapy, particularly immune checkpoint blockade, has transformed the therapeutic landscape of several GI cancers and HCC. Clinical trials evaluating immune checkpoint inhibitors, adoptive cell therapies, cancer vaccines, and immune-modulating agents, both as monotherapies and in combination with targeted therapy, chemotherapy, radiotherapy, and locoregional approaches, have demonstrated meaningful clinical benefit in subsets of patients. Nevertheless, clinical responses remain variable, immune-related toxicities pose challenges, and validated predictive biomarkers are limited.

This Special Issue aims to integrate basic, translational, and clinical research and highlight the studies describing the role and modulation of the immune microenvironment, advanced immunotherapy, and targeted gene therapy techniques to treat HCC as well as other GI cancers (including esophagus, stomach, pancreas, intestines, and colon), as well as the clinical implications/outcomes of the advanced therapeutic strategies on the patients’ populations along with clinical trials. By highlighting mechanistic discoveries alongside clinical trial data and real-world evidence, this collection seeks to bridge laboratory findings with clinical application and inform the development of more effective, personalized immunotherapy-based treatments.

This Special Issue aims to cover advanced immunotherapeutic strategies, translational insights, and clinical research developments in hepatocellular carcinoma and gastrointestinal cancers. Submissions may include, but are not limited to:

• Clinical trials of immunotherapies in HCC and GI cancers (phase I–IV);
• Real-world clinical outcomes and treatment optimization strategies;
• Biomarker-driven patient stratification and response prediction;
• Mechanisms of clinical response, resistance, and immune-related toxicity;
• Tumor immune microenvironment and its clinical implications;
• Combination strategies integrating immunotherapy with systemic or locoregional treatments;
• Translational studies linking preclinical models to clinical findings;
• Emerging immunotherapeutic modalities and next-generation immune targets;
• Cancer Vaccines;
• CAR-T and adoptive cell therapy.

Article types and fees:

This Special Issue accepts the following article types, unless otherwise specified in the Special Issue description:

• Original basic, clinical or translational research articles;
• Review articles (narrative or systematic);
• Epidemiology;
• Perspectives and hypothesis articles;
• Methods;
• General commentary.

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to authors, institutions, or funders.

Dr. Kaushik Banerjee
Guest Editor

Dr. Shayanki Lahiri
Dr. Lei Yang
Co-Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• hepatocellular carcinoma
• gastrointestinal cancers
• clinical immunotherapy
• immune checkpoint inhibitors
• tumor immune microenvironment
• biomarkers and precision oncology
• immunotherapy resistance
• immune-related adverse events
• combination therapy
• CAR-T and adoptive cell therapy
• cancer vaccines
• translational and clinical research
• clinical trials
• real-world evidence