Immunotherapy of Cancer Diseases
Immunotherapeutic strategies have been successfully utilized recently in the treatment of various malignancies. Increasing understanding of the interactions between the tumor and the host organism over the last few years has led to proposals of various promising therapeutic approaches. This overview briefly summarizes the basic principles of immunotherapy for cancer diseases.
The Immune System and Tumor Defense
It has been shown that the immune system plays a significant role in controlling tumorigenesis and tumor progression. It appears that the presence of lymphocytes infiltrating tumor tissue correlates with favorable prognosis in various types of malignancies. Particularly important is the presence of CD8+ cytotoxic T lymphocytes and the ratio between CD8+ effector T lymphocytes and CD4+/forkhead box P3+ regulatory T lymphocytes.
How T Lymphocytes Recognize Tumor Cells
On the surface of T lymphocytes, there is a set of T-cell receptors (TCR) that interact with antigenic peptides presented on the surface of cells. For adaptive immunity to respond to countless possible foreign antigens, T lymphocytes maintain a very diversified repertoire of different TCR configurations.
Under normal circumstances, T lymphocytes with various TCRs circulate in the bloodstream until they encounter a foreign peptide presented on the surface of cells due to infection or malignant transformation. Upon encountering the antigen, the lymphocyte is activated, undergoes clonal proliferation and expansion, and mounts a cytolytic response.
Tumors Can Escape Immune Surveillance
The innate and adaptive immune systems collaborate on immune surveillance of tumor processes. Dysfunctional tumor immune interactions are key for tumor development and metastatic processes. Tumors succeed in escaping immune processes through various mechanisms that lead either to impaired antigen recognition or to the creation of a highly immunosuppressive microenvironment within the tumor tissue.
Options for Immunotherapy of Oncological Diseases
New antitumor immunostimulatory therapies that utilize existing inefficient immune responses by targeting checkpoints in immune signaling pathways have shown interesting clinical activity in several tumor types. Most immunotherapeutic drugs currently in various stages of development can be broadly categorized into two groups:
- Drugs that target tumor immune escape by blocking negative regulatory signals (e.g., coinhibitory checkpoints and tolerogenic enzymes).
- Agents that directly stimulate immunogenic pathways (e.g., agonists of costimulatory receptors).
Other immunostimulatory strategies include substances that enhance antigen presentation (e.g., vaccines), the use of exogenous recombinant cytokines, oncolytic viruses, and cell therapies using native or modified antigen-competent immune cells.
Efficacy Is Influenced by Many Factors
However, the response rate of patients to immunotherapy is currently rather moderate, likely due to the heterogeneity of the tumor environment and the complexity and multiplicity of mechanisms by which tumors escape the immune response. Therefore, intensive research is ongoing into drugs targeting various mechanisms of immune tolerance and their combinations. The continuous development of predictive biomarkers and personalized precision-targeted immunotherapy should also help to increasingly improve treatment efficacy for individual patients.
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Source: Velcheti V., Schalper K. Basic overview of current immunotherapy approaches in cancer. Am Soc Clin Oncol Educ Book 2016; 35: 298–308, doi: 10.14694/EDBK_156572.
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