Journal of Hepatology and Gastrointestinal disorders
Open Access

Hepatocellular Carcinoma Adoptive Cell Therapy: CAR T Cells and Tumor-Infiltrating Lymphocytes

Craig Ghany^{* *}Correspondence: Craig Ghany, Department of Hepatology, University of Barcelona, Barcelona, Spain, Email:

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About the Study

Immunotherapy for Hepato Cellular Carcinoma (HCC) represents a significant advancement in oncology, emphasizing the strategic mislead of the immune system to recognize and destroy malignant cells. This therapeutic approach utilizes the inherent potential of the immune system to fight tumors while striving to overcome the immunosuppressive microenvironment that characterizes HCC. As the most common form of primary liver cancer, HCC raises a formidable challenge due to its complex pathogenesis, often associated with chronic liver diseases, and its resistance to conventional therapies. Central to the rationale for immunotherapy in HCC is the connection between tumor cells and the immune system. HCC tumors create an immunosuppressive context that facilitates their survival and progression. This environment is characterized by the presence of regulatory T cells, myeloid-derived suppressor cells, and an overexpression of immune checkpoint molecules such as Programmed Death-Ligand 1 (PD-L1). These factors collectively inhibit the activity of cytotoxic T lymphocytes, which are important for targeting and eliminating tumor cells. Immunotherapy aims to disrupt these immunosuppressive mechanisms, thereby reactivating the immune response against the tumor.

One of the primary strategies in immunotherapy is the use of immune checkpoint inhibitors. These agents block the inhibitory signals that dampen T cell activity, enabling a robust anti-tumor immune response. By targeting checkpoint molecules like PD-1, PD-L1, and Cytotoxic T Lymphocyte Antigen-4 (CTLA-4), these inhibitors maintain the functional capacity of T cells to attack HCC cells. Another promising approach involves adoptive cell therapy, which entails the engineering or enhancement of immune cells to target HCC specifically. This includes Chimeric Antigen Receptor (CAR) T cell therapy and Tumor-Infiltrating Lymphocyte (TIL) therapy. CAR T cell therapy involves modifying T cells to express receptors that recognize tumor-specific antigens, thereby directing them to eliminate HCC cells. TIL therapy capitalizes on the ability of naturally occurring immune cells to infiltrate tumors, amplifying their activity to potentiate an anti-tumor response.

Another aspect of immunotherapy is cytokine treatment, focusing on modulating the immune context to promote antitumor activity. Cytokines like Inter Leukin-2 (IL-2) and Inter Feron-Alpha (IFN-α) are utilized to enhance the proliferation and activity of immune cells. These therapies aim to shift the balance in the tumor microenvironment from immunosuppressive to immunostimulatory, thereby facilitating tumor control. Vaccination strategies also show potential in the stage of immunotherapy for HCC. Therapeutic vaccines aim to stimulate the immune system by presenting Tumor-Associated Antigens (TAAs) or Tumor-Specific Antigens (TSAs) to initiate an immune response. Such vaccines are designed to induce a long-lasting immunological memory, which may prevent recurrence and progression of the disease.

The Tumor Micro Environment (TME) in HCC is a critical determinant of the efficacy of immunotherapy. The TME is a complex ecosystem comprising cancer cells, stromal cells, immune cells, and extracellular components. It is often dominated by immunosuppressive elements, including Tumor- Associated Macrophages (TAMs) and regulatory T cells, which impede effective immune responses. Strategies to remodel the TME are important in improving immunotherapy's performance. This involves reprogramming TAMs, reducing the population of immunosuppressive cells, and enhancing the infiltration and activation of cytotoxic T cells. A major obstacle is tumor heterogeneity, since the varied genetic and phenotypic components of HCC might result in varying treatment outcomes. Furthermore, the liver’s intrinsic tolerogenic nature, which is important for maintaining immune homeostasis, can limit the efficacy of immunotherapeutic interventions. Biomarkers play an important role in predicting and monitoring the response to immunotherapy in HCC. Identifying reliable biomarkers can direct patient selection, enabling a more personalized approach to treatment. Biomarkers such as PD-L1 expression, tumor mutational burden, and immune cell infiltration are being analyzed to improve results and improve therapy approaches.