Cancer and immunity: relationship

Cancer and immunity: relationship

Section 1: Fundamentals of the immune system and its functioning

The immune system is a complex network of cells, tissues, organs and processes intended to protect the body from diseases. It performs this function by recognizing and destroying alien invasions, such as bacteria, viruses, fungi, parasites, as well as abnormal cells, including cancer. For adequate protection, the immune system uses both congenital and adaptive mechanisms.

1.1. Inborn immunity: the first line of defense

Congenital immunity is the first line of protection of the body, which reacts quickly and nonspecific to a wide range of threats. It is present from birth and does not require preliminary contact with the antigen for activation. Key components of congenital immunity include:

• Physical barriers: The skin, the mucous membranes of the respiratory tract, the gastrointestinal tract and the genitourinary system serve as a physical barrier that prevents the penetration of pathogens. These barriers also contain chemicals, such as lysozyme in tears and saliva, which have antimicrobial properties.

• Cells of congenital immunity:

  • Macrophages: Fagocytes that absorb and destroy pathogens, as well as dead cells. They also emit cytokines, signal molecules that activate other cells of the immune system and contribute to inflammation.

  • Neutrophils: The most common blood blood cells, which quickly migrate to the place of infection, where they phagocytes and destroy pathogens. They also participate in the formation of pus.

  • Dendritic cells: The “guards” of the immune system that constantly scan the environment for the presence of antigens. After the capture of the antigen, they migrate to the lymph nodes, where they represent it to T-cells, activating adaptive immunity.

  • Natural killers (NK cells): Cells capable of recognizing and destroying infected or cancer cells without needing preliminary sensitization. They use various mechanisms, including the release of cytotoxic granules containing perfors and granzims that cause apoptosis (programmable cell death) of target cells.

  • Mastocytes: Cells localized in tissues releasing histamine and other inflammation mediators in response to allergens or infection. They play an important role in allergic reactions.

• Protein systems:

  • Complement: The blood protein system, which is activated according to the cascade mechanism, leading to opsonization (coating of pathogens with antibodies or components of complement, facilitating their phagocytosis), inflammation and lysis (destruction) of pathogens.

  • Cytokines: A wide range of signal molecules that regulate the activity of immune cells. These include interleukins, interferons, tumor necrosis factors (TNF) and Hemokina.

1.2. Adaptive immunity: targeted and long -term protection

Adaptive immunity is a later and specific protection line that develops in response to specific antigens. It is characterized by a memory that allows the body to respond faster and more efficiently to the re -effect of the same antigen. Adaptive immunity includes two main types of answers: cellular and humoral.

• Cellular immunity: Mediated by T-lymphocytes.

  • T-highpers (CD4+ T cells): They regulate the immune response, secreting cytokines that activate other immune cells, including B cells and cytotoxic T cells. Various T-Helper subtypes, such as Th1, Th2 and Th17, specialize in various types of immune answers.

  • Cytotoxic T cells (CD8+ T cells): Infected or cancer cells are directly destroyed, recognizing antigens presented on the surface of these cells. They use mechanisms similar to NK cells, such as the release of punch and Granzima.

  • Regulatory T cells (Treg): The immune response is suppressed, preventing autoimmune diseases and excessive inflammation.

• Humoral immunity: Mediated by b-lymphocytes.

  • B cells: They recognize antigens and differentiate into plasma cells that produce antibodies.

  • Antibodies (immunoglobulins): Proteins that are associated with antigens, neutralizing them or marrying them to destroy other immune cells. There are various antibodies, such as IGG, IGM, IGA, IGE and IGD, each of which has its own function.

1.3. Antigens and recognition of antigens

Antigen is any substance that can be recognized by the immune system and cause an immune response. Antigens can be proteins, carbohydrates, lipids or nucleic acids. Immune cells recognize antigens using receptors located on their surface.

• T-cell receptors (TCR): T-cell receptors recognizing antigens presented in combination with molecules of the main histocompatibility complex (MHC) on the surface of other cells.

• B-cell receptors (BCR): Receptors on B cells that recognize antigens in free form.

Section 2: Mechanisms of immune supervision against cancer

The immune system plays an important role in preventing the development of cancer through a process called immune supervision. This process includes recognition and destruction of cancer cells before they have time to form a tumor.

2.1. Recognition of cancer cells by the immune system

Cancer cells often express abnormal antigens that are not present on normal cells. These antigens can be:

• Mutant proteins: Proteins encoded by mutated genes that are characteristic of cancer cells.

• Oncofetal antigens: Proteins, which are usually expressed only during embryonic development, but can be re -activated in cancer cells.

• Squirrels super -expert with cancer cells: Proteins that are expressed in normal cells at a low level, but are significantly increased in cancer cells.

These antigens can be recognized by the immune system, activating cellular and humoral immune answers. Dandritic cells play a key role in the capture of these antigens and the presentation of their T-cells in the lymph nodes, initiating an immune response.

2.2. Effector mechanisms of the immune response against cancer

After activation, immune cells use various mechanisms to destroy cancer cells:

• Cytotoxic T cells (CD8+ T cells): Cancer cells are directly destroyed, recognizing antigens presented on the surface of these cells. They use mechanisms similar to NK cells, such as the release of punch and Granzima.

• Natural killers (NK cells): The cancer cells are recognized and destroyed, which have lost the expression of MHC class I molecules, which often occurs in cancer cells to avoid recognition of T-cells.

• Antibodies: They are associated with antigens on the surface of cancer cells, neutralizing them or marrying them to destroy other immune cells, such as macrophages (antibody -dependent cell cytotoxicity – ADCC).

• Macrophages: Cancer cells are phagocytized, especially those that are oponized with antibodies or components of complement. They also emit cytokines that activate other cells of the immune system and contribute to antitumor immunity.

2.3. The role of cytokines in antitumor immunity

Cytokins play a critical role in the regulation of an antitumor immune response. Some cytokines, such as Interleukin-2 (IL-2), Interferon-Gamma (IFN-γ) and factor of tumor-alpha necrosis (TNF-α), have antitumor activity, stimulating the proliferation and activity of immune cells. Other cytokines, such as Interleukin-10 (IL-10) and the transforming factor of growth-Beta (TGF-β), can suppress the immune response and contribute to the growth of the tumor. The balance between pro- and anti-inflammatory cytokines is crucial for effective antitumor immunity.

Section 3: Evasion of cancer cells from the immune response: immunosuppression mechanisms

Despite immune supervision, cancer cells often develop mechanisms that allow them to evade the immune response and contribute to the growth of the tumor. These immunosuppression mechanisms can be both cellular and molecular.

3.1. Loss or decrease in expression of MHC antigens class I

Class I MHC molecules are necessary for the presentation of antigens to T-cells. Cancer cells can lose or reduce the expression of these molecules to avoid recognition by cytotoxic T cells. This mechanism allows cancer cells to “hide” from the immune system.

3.2. Immune checkpoints expression

Immune control points are molecules that regulate the activity of immune cells, preventing excessive immune answers and autoimmune. Cancer cells can use immune control points such as PD-1/PD-L1 and CTLA-4, to suppress the immune response.

• PD-1/PD-L1: PD-1 (Programmed Death-1) is a receptor expressed on T cells. PD-L1 (Programmed Death-Ligand 1) is a Ligand PD-1, which can be expressed on cancer cells and other cells of the immune microcraction of the tumor. The PD-1 interaction with PD-L1 leads to inhibiting T-cells, reducing their ability to destroy cancer cells.

• CTLA-4: CTLA-4 (Cytotoxic T-Lymphocyte-SSOSOCIETED PROTEIN 4) is another receptor expressed on T-cells that competes with CD28 for connecting with B7 molecules on antigen-representative cells. The CTLA-4 interaction with B7 molecules leads to inhibiting T cells.

3.3. The secretion of immunosuppressive cytokines

Cancer cells can secrete immunosuppressive cytokines, such as IL-10 and TGF-β, which suppress the activity of immune cells and contribute to the growth of the tumor. These cytokines can inhibit the proliferation and function of T-cells and NK cells, as well as contribute to the differentiation of regulatory T-cells (Treg).

3.4. A set of immunosuppressive cells in tumor micro -infection

Micro -anguing of the tumor is a complex environment consisting of cancer cells, immune cells, stromal cells and extracellular matrix. Cancer cells can attract immunosuppressive cells to the micro -infection of the tumor, such as:

• Myeloid Suppressor cells (MDSC): A group of heterogeneous myeloid cells, which inhibit the activity of T cells and NK cells. They distinguish immunosuppressive factors, such as Arginase and nitrogen oxide.

• Regulatory T cells (Treg): The immune response is suppressed, preventing autoimmune diseases and excessive inflammation. In micro -infection, Treg tumors can suppress the antitumor immune response.

• Macrophages associated with a tumor (TAM): Macrophages, which are polarized towards the phenotype M2, which contributes to the growth of the tumor, angiogenesis and metastasis.

3.5. Induction of immunological tolerance

Immunological tolerance is a condition in which the immune system does not respond to a specific antigen. Cancer cells can induce immunological tolerance to their antigens, preventing their recognition and destruction of the immune system. This can happen due to various mechanisms, such as the presentation of antigens in the absence of costimulating signals or the induction of regulatory T cells.

Section 4: Cancer Immunotherapy: Using the immune system to combat cancer

Cancer immunotherapy is a treatment strategy that uses the immune system to combat cancer. There are various types of immunotherapy that are aimed at various aspects of the immune system.

4.1. Immune control points inhibitors

Inhibitors of immune control points are drugs that block the interaction between immune control points and their ligands, releasing T-cells from inhibition and allowing them to attack cancer cells. Examples of immune control points inhibitors include:

• Anti-PD-1 Antibodies: Pembrolizumab, levels of level.

• Anti-PD-L1 antibodies: Athemiazumab, Durvalumab, Avelumab.

• Anti-CTLA-4 antibodies: Yepilimumab.

Inhibitors of immune control points showed the effectiveness in the treatment of various types of cancer, including melanoma, lung cancer, kidney cancer and Hodgkin lymphoma.

4.2. Car-T-cell therapy

CAR-T-cell therapy is a form of cell therapy in which the patient T-cells are genetically modified for the expression of a chimeric antigenic receptor (CAR), which recognizes a specific antigen on the surface of cancer cells. Then the modified T cells are propagated in the laboratory and entered back to the patient, where they attack and destroy cancer cells. Car-T-cell therapy showed high efficiency in the treatment of some types of leukemia and lymphoma.

4.3. Therapeutic vaccines against cancer

Therapeutic vaccines against cancer are designed to stimulate an immune response against cancer cells. They can contain antigens of cancer cells, such as mutant proteins or oncofetal antigens, as well as adjuvantes that enhance the immune response. Therapeutic vaccines against cancer can be personalized, that is, designed specifically for a particular patient based on antigens expressed by his cancer tumor.

4.4. Oncolytic viruses

Oncolytic viruses are viruses that selectively infect and destroy cancer cells without damaging normal cells. After infection of the cancer cell, the virus multiplies and causes its lysis (destruction), releasing more viruses that infect other cancer cells. Infected cancer cells can also release antigens that stimulate the immune response against the tumor.

4.5. Cytokine therapy

Cytokine therapy uses cytokines, such as IL-2 and IFN-α, to stimulate the immune response against cancer. IL-2 can stimulate the proliferation and activity of T-cells and NK cells, and the IFN-α can increase the expression of MHC class I molecules on cancer cells, making them more susceptible to recognition of T-cells.

4.6. Adoptive Cell Transfer)

Adoptive cell therapy involves the removal of the patient’s immune cells, such as T cells or NK cells, from the body, cultivating and activating them in the laboratory, and then introducing them back to the patient. This method is used to increase the number and activity of immune cells that can attack cancer cells. The transfer of lymphocytes that infiltrate the tumor (TIL) is a variety of adoptive cell therapy, in which T-cells extracted directly from the patient’s tumor are propagated and entered back to the patient.

Section 5: Factors affecting the immune response against cancer

The effectiveness of the immune response against cancer can be due to various factors, including the genetic characteristics of the patient, the type of cancer, the stage of the disease, the previous treatment and lifestyle.

5.1. Genetic factors

Genetic polymorphisms in genes encoding the components of the immune system can affect the patient’s ability to develop an effective immune response against cancer. For example, polymorphisms in the MHC genes can affect the spectrum of antigens that can be represented by T-cells.

5.2. Type of cancer and stage of the disease

Different types of cancer deviate differently from the immune response. Some types of cancer, such as melanoma and lung cancer, have more mutations than other types of cancer, which makes them more immunogenic and more susceptible to immunotherapy. The stage of the disease can also affect the immune response. In the later stages of cancer, the immune system can be exhausted or suppressed, which reduces the effectiveness of immunotherapy.

5.3. Preceding treatment

Some methods of cancer treatment, such as chemotherapy and radiation therapy, can suppress the immune system, reducing the effectiveness of immunotherapy. Other treatment methods, such as targeted therapy, can modulate the immune response, increasing or reducing the effectiveness of immunotherapy.

5.4. Life

Life lifestyle factors, such as diet, physical exercises and smoking, can affect the immune system. Healthy nutrition, regular physical exercises and smoking refusal can strengthen the immune system and increase the efficiency of immunotherapy.

5.5. Age

With age, the immune system weakens, which makes the elderly more susceptible to cancer and less susceptible to immunotherapy. This process, known as immunostation, is characterized by a decrease in the quantity and function of T cells and NK cells, as well as an increase in the number of immunosuppressive cells.

Section 6: future areas of research in the field of cancer immunotherapy

The cancer immunotherapy area is developing rapidly, and at present numerous studies are conducted aimed at improving the efficiency and expanding the use of immunotherapy.

6.1. Combined immunotherapy

Combined immunotherapy involves the use of two or more immunotherapeutic approaches simultaneously or sequentially. For example, immune control points inhibitors can be combined with therapeutic vaccines against cancer or oncolytic viruses to enhance the immune response. Combined immunotherapy may also include a combination of immunotherapy with other types of cancer treatment, such as chemotherapy or radiation therapy.

6.2. Personalized immunotherapy

Personalized immunotherapy involves the development of individual immunotherapeutic approaches for each patient based on the genetic and immunological characteristics of his cancer tumor. This may include the development of personalized therapeutic vaccines against cancer or Car-T-cell therapy aimed at specific antigens expressed by the patient’s cancerous tumor.

6.3. Targeting of tumor micro -infection

Micro -angle of the tumor plays an important role in evading cancer cells from the immune response. Targeting of tumor microoruscation can improve the effectiveness of immunotherapy. This may include inhibition of immunosuppressive cells, such as MDSC and Treg, or modify the extracellular matrix to facilitate the penetration of immune cells into the tumor.

6.4. Development of new immune control points

New immune control points are identified, which can be targeted to strengthen the immune response against cancer. Research is aimed at developing inhibitors of these new immune control points.

6.5. Improving the delivery of immunotherapeutic drugs

Improving the delivery of immunotherapeutic drugs to the tumor can increase their effectiveness and reduce side effects. This may include the use of nanoparticles or other delivery systems for targeting immunotherapeutic drugs to the tumor.

6.6. Using artificial intelligence and machine learning

Artificial intelligence (AI) and machine learning (MO) are used to analyze large amounts of data obtained from patients with cancer in order to detect biomarkers who may predict the response to immunotherapy. AI and MO are also used to develop new immunotherapeutic strategies.

Section 7: Difficulties and problems in cancer immunotherapy

Despite promising results, cancer immunotherapy is faced with a number of difficulties and problems.

7.1. Immuno -mediated side effects

Immunotherapy can cause immuno -mediated side effects that occur as a result of excessive activation of the immune system. These side effects can affect any organ or body system and can be serious or even fatal. Treatment of immuno -mediated side effects may include the use of corticosteroids or other immunosuppressive drugs.

7.2. Primary and acquired resistance to immunotherapy

Not all patients respond to immunotherapy, and some patients over time develops resistance to immunotherapy. Primary stability is when the patient does not respond to immunotherapy from the very beginning. Acquired stability is when the patient initially reacts to immunotherapy, but ceases to react over time. Mechanisms of resistance to immunotherapy are complex and may include loss of antigens expression, the expression of immune control points, or the presence of immunosuppressive cells in the micro -infection of the tumor.

7.3. Lack of reliable forecast biomarkers

The absence of reliable forecast biomarkers makes it difficult to determine which patients are most likely to react to immunotherapy. Currently, various biomarkers are used, such as PD-L1 expression and the mutational load of the tumor, but they do not always precisely predict the response to immunotherapy. Additional studies are needed to identify new and more reliable forecast biomarkers.

7.4. High cost of immunotherapy

Immunotherapy is an expensive treatment method, which limits its accessibility for many patients. The search for ways to reduce the cost of immunotherapy is crucial for ensuring its accessibility for all patients in need of it.

7.5. Difficulties in the development of personalized immunotherapy

The development of personalized immunotherapy is a complex and laborious task. This requires the identification of specific antigens expressed by the patient’s cancerous tumor, as well as the development of an immunotherapy approach aimed at these antigens. More effective and economical methods for developing personalized immunotherapy are needed.

In conclusion, the relationship between cancer and immunity is complex and multifaceted. The immune system plays an important role in preventing the development of cancer through immune supervision. However, cancer cells often develop mechanisms that allow them to evade the immune response. Cancer immunotherapy uses the immune system to combat cancer and showed promising results in the treatment of various types of cancer. Despite the progress achieved, cancer immunotherapy is faced with a number of difficulties and problems that require further research. Improving the understanding of the relationship between cancer and immunity and the development of more effective immunotherapeutic strategies are crucial to improve the treatment of patients with cancer.