Cancer and immunity: immunotherapy

RAC IMMUNITET: IMMUNOTERAPY – A Deep Dive

I. Fundamentals of relationships: cancer and immune system

1. Immune system: body guard:

   • Review of the components of the immune system: congenital and adaptive immunity.
   • The role of immune cells: T cells, B cells, NK cells, dendritic cells, macrophages.
   • Cytokins: signal molecules that regulate the immune response.
   • Mechanisms for the destruction of pathogens: phagocytosis, cytotoxicity, complement activation.
   • Immune supervision: constant monitoring of the body for abnormal cells.

2. Cancer development: elimination of immunity:

   • Mechanisms for the formation of cancer cells: mutations, epigenetic changes.
   • Characteristics of cancer cells: uncontrolled growth, metastasis, angiogenesis.
   • A change in tumor micro -inflection: attracting immunosuppressive cells, creating barriers to an immune response.
   • Immune editing: The process during which the immune system destroys the most immunogenic cancer cells, leaving less susceptible options.
   • The role of chronic inflammation in the development of cancer: stimulation of the proliferation of cells, angiogenesis and immunosuppression.

3. The mechanisms of elimination of cancer from the immune response:

   • Loss or decrease in the expression of MHC antigens class I: a decrease in the ability of cancer cells to represent antigens of T-cells.
   • The expression of immune control points (for example, PD-L1, CTLA-4): suppression of the activity of T-cells.
   • The secretion of immunosuppressive cytokines (for example, TGF-β, IL-10): inhibiting immune cells and attracting regulatory T-cells (TREGS).
   • A set of immunosuppressive cells in tumor micro-infection: Tregs, myeloid suppressor cells (MDSCS), tumor-assed macrophages (TAMS).
   • Creation of physical barriers: the formation of a dense stroma that prevents the penetration of immune cells.
   • Antigenic modulation: change or masking of antigens on the surface of cancer cells to avoid recognition of the immune system.
   • Induction of apoptosis of immune cells: cancer cells can distinguish molecules that cause the death of immune cells.
   • Metabolic deficiency: cancer cells actively consume nutrients, depriving immune cells of energy and the necessary resources.

II. Immunotherapy: a new approach to cancer treatment

1. Review of immunotherapy strategies:

   • Principles of immunotherapy: stimulation of its own immune system to combat cancer.
   • The main types of immunotherapy: immune control points inhibitors, car-T cell therapy, oncolithic viruses, cancer vaccines, cytokine therapy.
   • Advantages of immunotherapy: potential for a long response, exposure to a wide range of cancer cells, less side effects compared to chemotherapy (in some cases).
   • Restrictions on immunotherapy: only in a particular group of patients, the possibility of developing autoimmune side effects, and high cost.

2. Inhibitors of immune control points (ICI):

   • The mechanism of action: blocking proteins that suppress the activity of T-cells (for example, PD-1, PD-L1, CTLA-4).
   • Preparations: pembrolyzumab, nivolumab, athelesolyzumab, Ipilimumab, durvalumab, Tsemblimab.
   • Types of cancer in which ICIs showed effectiveness: melanoma, lung cancer, kidney cancer, Hodgkin lymphoma, bladder cancer, head and neck cancer, liver cancer, liver cancer, and microsatelite instability (MSI-H) cancer.
   • Side effects: autoimmune reactions (colitis, pneumonitis, hepatitis, endocrinopathy, dermatitis).
   • Side effects management: corticosteroids, immunosuppressors.
   • Biomarkers for predicting the response to ICI: PD-L1 Expression, microsatellite instability (MSI-H), mutation load of the tumor (TMB).
   • Combinations of ICI with other treatment methods: chemotherapy, radiation therapy, targeted therapy.
   • New immune control points: TIM-3, LAG-3, TIGIT.
   • ICI clinical research: results and prospects.

3. Car-T-cell therapy:

   • The mechanism of action: modification of the patient T-cells for recognition and destruction of cancer cells.
   • The CAR-T-cell therapy process: the patient’s fence in the patient, genetic modification, reproduction in the laboratory, and introduction back to the patient.
   • Types of Car-T cells: CD19-Car-T (for the treatment of B-cell lymphomas and leukemia), BCMA-Car-T (for the treatment of multiple myeloma).
   • Preparations: Tyssengenleisel, Axycabtagen Siloleisel, Brexukabtagen Autolyusel.
   • Indications: recurrent or refractory B-cell lymphomas, acute lymphoblastic leukemia, multiple myeloma.
   • Side effects: cytokine release syndrome (SVC), neurotoxicity, cytopenia.
   • Control of side effects: Tocilizumab, corticosteroids.
   • Prospects of CAR-T-cell therapy: Development of CAR-T cells against other types of cancer, improving safety and efficiency of CAR cells.
   • Allogene CAR-T cells (“Off-The-SHELF” CAR-T): the use of Donor T-cells to create a Car-T cells, which allows you to accelerate the treatment process and reduce the cost.
   • Solid tumors and Car-T: Development of strategies for overcoming obstacles, such as limited penetration of Car-T cells into the tumor and immunosuppressive microtrape of the tumor.

4. Oncolytic viruses:

   • The mechanism of action: viruses selectively infected and destroying cancer cells.
   • The mechanisms of the action of oncolytic viruses: direct lysis of cancer cells, stimulation of the immune response against cancer.
   • Preparations: Talimogen camp (T-VEC) (for the treatment of melanoma).
   • Types of cancer in which oncolytic viruses can be effective: melanoma, glioblastoma, liver cancer.
   • Side effects: flu -like symptoms.
   • A combination of oncolytic viruses with other methods of immunotherapy: increasing the effectiveness of treatment.
   • Development of new oncolytic viruses: improvement of selectivity, safety and efficiency.
   • Genetically modified oncolithic viruses: embedding genes encoding immunostimulating cytokines to enhance the immune response.

5. Cancer vaccines:

   • The mechanism of action: stimulation of the immune response against cancer cells by introducing antigens specific to cancer.
   • Types of cancer vaccines: peptide vaccines, cell vaccines, DNA vaccines, RNA vaccines.
   • Examples of cancer vaccines: Sipuleusel-T (for the treatment of prostate cancer).
   • Personalized cancer vaccines: creating vaccines based on unique mutations in the patient’s tumor.
   • Problems in the development of cancer vaccines: weak immunogenicity, immunosuppressive micro -inflection of the tumor.
   • Strategies to improve the effectiveness of cancer vaccines: the use of adjuvants, a combination with other immunotherapy methods.
   • Neoantigenic vaccines: aiming on a mutation unique to the patient’s tumor, which provides a more specific immune response.
   • Clinical studies of cancer vaccines: results and prospects.

6. Cytokine therapy:

   • The mechanism of action: the use of cytokines to stimulate an immune response against cancer.
   • The cytokines used in cancer therapy: Interleukin-2 (IL-2), Interferon-alpha (IFN-α).
   • Types of cancer in which cytokine therapy can be effective: melanoma, kidney cancer.
   • Side effects: capillary leakage syndrome (SKU), flu -like symptoms.
   • Restrictions on cytokine therapy: high toxicity, unpredictable answer.
   • Modern approaches to cytokine therapy: the use of low doses of cytokines, the development of cytokines with improved selectivity and safety.
   • Engineering cytokines: modification of cytokines to increase their activity and reduce side effects.
   • Cytokine agonists: development of molecules that simulate the effect of cytokines, but with an improved security profile.

III. Factors affecting the effectiveness of immunotherapy

1. Micro -angle of the tumor:

   • The role of immunosuppressive cells (Tregs, MDSCS, TAMS): inhibiting the immune response.
   • Changing the metabolism of the tumor: a decrease in the availability of nutrients for immune cells.
   • Hypoxia in the tumor: a decrease in the activity of immune cells.
   • Strategies for modulation of tumor micro -infection: inhibiting immunosuppressive cells, improving tumor vascularization, and normalization of tumor metabolism.
   • The transformation of “cold” tumors into “hot”: increased tumor infiltration with immune cells.
   • The role of microbiota: the effect on the composition of microbiota to improve response to immunotherapy.

2. Genetic factors:

   • Tumor mutation load (TMB): correlation with an answer to ICI.
   • Microsatelite instability (MSI-H): predictor response to ICI.
   • Class I MHC genes: the role in the presentation of antigens T-cells.
   • Genes participating in the immune response: influence on the effectiveness of immunotherapy.
   • Epigenetic modifications: the impact on the expression of genes involved in the immune response.
   • Genomic analysis for personalization of immunotherapy: identification of patients who are most likely responding to immunotherapy.

3. The condition of the patient’s immune system:

   • Age: Impact on the immune function.
   • Previous treatment: impact on the immune response.
   • Related diseases: impact on the immune function.
   • Immunosuppressive drugs: inhibiting an immune response.
   • Assessment of the patient’s immune competence before the onset of immunotherapy: determining the possibility of an effective immune response.
   • Strategies to improve the patient’s immune system: the use of immunostimulating drugs, vaccination.

4. Biomarkers to predict an answer to immunotherapy:

   • PD-L1 Expression: predictor response to ICI (in some cases).
   • The mutation load of the tumor (TMB): the predictor response to ICI.
   • Microsatelite instability (MSI-H): predictor response to ICI.
   • Tumor infiltration with immune cells: correlation with an answer to immunotherapy.
   • Cytokine profile: determination of cytokines related to the response to immunotherapy.
   • Proper citometry: analysis of immune cells in the blood and tumors.
   • Development of new biomarkers to predict an response to immunotherapy: Improving the selection of patients who most likely will respond to treatment.
   • Liquid biopsy: Analysis of DNA, RNA and proteins in the blood to monitor a response to immunotherapy.

IV. Immunotherapy: Future of cancer treatment

1. Combinations of immunotherapy with other treatment methods:

   • Chemotherapy: synergism with immunotherapy.
   • Radiation therapy: stimulation of the immune response.
   • Targeted therapy: Strengthening the immune response.
   • Surgical treatment: tumor removal and stimulation of an immune response.
   • Development of rational combinations: determination of optimal combinations for each type of cancer.
   • The sequence of application of treatment methods: determining the optimal sequence for maximizing the effectiveness of treatment.

2. Personalized immunotherapy:

   • Development of vaccines based on unique mutations in the patient’s tumor (non -antgene vaccines).
   • The selection of immunotherapy based on the genetic profile of the tumor.
   • Adaptive immunotherapy: Change in treatment depending on the response of the patient.
   • Using large data and artificial intelligence: to analyze patients about patients and predict a response to immunotherapy.
   • Integration of genomics, proteomics and metabolomics: to create a comprehensive tumor profile and predict an response to immunotherapy.

3. Overcoming resistance to immunotherapy:

   • Identification of resistance mechanisms: determination of factors leading to inefficiency of immunotherapy.
   • Development of strategies to overcome resistance: inhibiting immunosuppressive mechanisms, stimulation of an immune response.
   • The use of new immune control points: TIM-3, LAG-3, TIGIT.
   • Development of Car-T cells resistant to immunosuppression.
   • Modulation of tumor micro -infection: Improving the penetration of immune cells into the tumor.

4. Development of new types of immunotherapy:

   • Cell therapy: Development of new types of immune cells to combat cancer.
   • Gene therapy: modification of immune cells to enhance their antitumor activity.
   • Nanotechnology: the use of nanoparticles for the delivery of immunostimulating agents to the tumor.
   • Artificial intelligence: the use of artificial intelligence to develop new types of immunotherapy.

5. Improving the safety of immunotherapy:

   • Development of methods to prevent autoimmune side effects.
   • The use of more selective immunotherapeutic drugs.
   • Development of biomarkers for predicting the development of side effects.
   • Personalized monitoring of patients receiving immunotherapy.
   • Development of new methods for managing side effects.

V. specific types of cancer and immunotherapy: current achievements and future directions.

1. Melanoma:

   • The role of ICI (Anti-CTLA-4, Anti-PD-1) in the treatment of metastatic melanoma.
   • The combination ICI with target therapyey (Braf, MEK Ingibitors).
   • Oncolytic viruses (T-VEC) for the treatment of local-fan-toned melanoma.
   • Prospects for vaccines against melanoma.
   • Clinical studies of new strategies for immunotherapy melanoma.

2. Lung cancer:

   • ICI (Anti-PD-1, Anti-PD-L1) in the treatment of non-alcohol cancer of the lung (NMRL) and small cell cancer of the lung (MRL).
   • Biomarkers for predicting the response to ICI (PD-L1 Expression, TMB).
   • Combination of ICI with chemotherapy and radiation therapy.
   • Car-T-cell therapy of lung cancer: challenges and prospects.
   • Development of vaccines against lung cancer.

3. Kidney cancer:

   • ICI (Anti-PD-1, Anti-CTLA-4) in the treatment of metastatic renal cell cancer (PKR).
   • Combination of ICI with targeted therapy (anti-VEGF).
   • Prospects for vaccines against kidney cancer.
   • Clinical studies of new kidney cancer immunotherapy strategies.

4. Breast cancer:

   • ICI (anti-PD-L1) in the treatment of three times negative breast cancer (TNTRMZH).
   • ICI studies for other subtypes of breast cancer.
   • CAR-T-cell therapy of breast cancer: early studies.
   • Development of vaccines against breast cancer.
   • Combinations of immunotherapy with hormonal therapy.

5. Tolstoy Cancer:

   • ICI (Anti-PD-1) in the treatment of cancer of the colon with microsaletic instability (MSI-H).
   • ICI studies with microselly stability (MSS) of colon cancer.
   • Development of vaccines against colon cancer.
   • Modulation of microbiots to improve response to immunotherapy with colon cancer.

6. Lymphomas:

   • ICI (anti-PD-1) in the treatment of Hodgkin lymphoma.
   • CAR-T-cell therapy B-cell lymphom.
   • ICI studies at other types of lymph.
   • Development of vaccines against lymph.

7. Glioblastoma:

   • The complexity of immunotherapy of glioblastoma due to immunosuppressive micro-infection.
   • ICI studies under glioblastoma.
   • Oncolytic viruses for the treatment of glioblastoma.
   • Car-T-cell therapy of glioblastoma: challenges and prospects.

8. Other types of cancer:

   • A review of the use of immunotherapy for other types of cancer (for example, prostate cancer, ovarian cancer, stomach cancer).
   • Clinical studies of immunotherapy for rare types of cancer.

VI. The role of the patient in immunotherapy

1. Understanding immunotherapy: The importance of the patient’s awareness of the principles of action, side effects and expected immunotherapy results.
2. Symptoms message: The patient’s active participation in the identification and message about any side effects for the timely take measures.
3. Support for a healthy lifestyle: The importance of a healthy diet, physical activity and rejection of smoking to maintain the immune system.
4. Psychological support: The role of psychological support in the treatment of cancer and immunotherapy.
5. Making decisions together with a doctor: The importance of the patient’s active participation in decision -making on the treatment and discussion of all options with a doctor.

VII. Conclusion:
The landscape of cancer treatment is constantly evolving, with immunotherapy standing at the forefront of innovation. While challenges remain in predicting response, overcoming resistance, and managing side effects, ongoing research and clinical trials are steadily expanding the reach and effectiveness of these therapies. The future of cancer treatment is likely to involve a combination of immunotherapy with other modalities, personalized approaches based on individual tumor characteristics, and a greater emphasis on improving patient outcomes and quality of life. Continued research and collaboration are essential to realize the full potential of immunotherapy in the fight against cancer.