Our Body’s Own Natural Immunological Battle Against Cancers

 

 In the body it was found that micro cancers or cellular cancers can already persist for years before cancer becoming clinically apparent. This latency period is influenced by the slow growth of cancer cells, immune surveillance, dormancy, genetic changes, and the span several years to decades.

It is possible for scientists to develop therapeutic strategies that mimic the body's own natural immunological systems to fight cancer.

Before that, let’s have a look at how the body naturally fights micro cellular cancers all the time. The time period before micro cellular cancers lurking in the body before they manifest themselves into full grown clinical cancer may take as long as 30 – 50 years, thanks to our wonderful immunological surveillance and its constant attack.  

The immune system against cancers is slightly different from those for infectious diseases since the body has to deal with its own malignancy, and not foreign agents from outside. Nevertheless, the same immune system plays a crucial role in recognizing and eliminating cancer cells through a process known as cancer immunosurveillance.

This involves both innate and adaptive immune mechanisms designed to detect and destroy abnormal cells that may become cancerous. The immunological mechanism against cancer is its innate immune response by releasing natural killer (NK) cells. These cells can recognize and kill cancer cells without prior sensitization. They identify stressed or abnormal cells by the absence of MHC class I molecules, which are often downregulated in cancer cells. The way NK cells do this is to release perforin and granzymes, which induce apoptosis (programmed cell death) in the target cell. Tumour-Associated Macrophages (TAMs) are also released.  These can have dual roles. M1 macrophages are pro-inflammatory and can kill tumour cells, while M2 macrophages may do the opposite by promoting tumour growth and suppressing the immune response.

The body response to cancer also involves phagocytosis by macrophages and cytokine production. Macrophages can engulf cancer cells and release cytokines that stimulate other immune cells. There are also the dendritic cells (DCs) and its antigen presentation where the DCs capture tumour antigens and present them to T cells, initiating an adaptive immune response. Activation of T Cells causes the presentation of antigens along with costimulatory signals for DCs to activate T cells to target and kill cancer cells. Furthermore, the body also has a complementary system that causes direct killing by directly lysing the tumour cells through the formation of the membrane attack complex (MAC). These include:

Opsonization to enhance phagocytosis of cancer cells by coating them with complement proteins.

Adaptive immune response to cancer T Cells involving cytotoxic T lymphocytes (CTLs or CD8+ T Cells) works by:

Recognition of tumour antigens causes CTLs recognition of specific antigens presented by MHC class I molecules on cancer cells that activate the killing mechanism.  Once activated, CTLs release perforin and granzymes that induce apoptosis in cancer cells.

Memory T Cells provide long-term immunity and can quickly respond to cancer cells if they reappear.

Helper T Cells (CD4+ T Cells) are there to support CTLs and B Cells. Helper T cells produce cytokines that aid the activation and proliferation of CTLs and B cells.

Regulation of immune response helps maintain a robust immune response against cancer cells. B cells can produce antibodies specific to tumour antigens.

Antibody-mediated immunity coats cancer cells through opsonization marking them for destruction by phagocytes.

NK cells and other effector cells can recognize antibody-coated cancer cells and kill them through antibody-dependent cellular cytotoxicity (ADCC).  

The interaction between the immune system and cancer cells can be described by the concept of immunoediting, which includes three phases:

1. Elimination:

The immune system detects and destroys cancer cells before they can establish a tumour.

2. Equilibrium:

Some cancer cells may survive initial immune attacks and enter a state of dormancy. During this phase, the immune system controls tumour growth, but the cancer cells are not completely eradicated.

3. Escape:

Cancer cells can acquire mutations that allow them to evade the immune system, leading to tumours progression and metastasis. Mechanisms of immune evasion include:

Downregulation of MHC molecules reduces the ability of T cells to recognize cancer cells by secretion of immunosuppressive molecules such as TGF-beta, IL-10, and VEGF, which inhibit the function of immune cells.

Expression of immune checkpoint molecules such as PD-L1, which interact with inhibitory receptors on T cells (like PD-1) to suppress their activity.

In terms of cancer treatment other than by surgery, chemotherapy, and radiation scientists having learnt these strategies briefly explained above in this essay, they  can now consider using cancer immunotherapy to mimic the body's own ability to fight cancer.

In order to enhance the immune system's ability to fight cancer, scientists have developed several immunotherapeutic strategies to help mimic the body These are:

1. Immune Checkpoint Inhibitors such as:

CTLA-4 Inhibitors: Block the CTLA-4 receptor on T cells, enhancing their activation.

PD-1/PD-L1 Inhibitors: Block the interaction between PD-1 on T cells and PD-L1 on cancer cells, preventing immune suppression.

2. Adoptive Cell Transfer:

CAR-T Cell Therapy: T cells are extracted from the patient, genetically engineered to express chimeric antigen receptors (CARs) that specifically target tumour antigens, and then reinfused into the patient.

3. Cancer Vaccines:

Preventive Vaccines: Such as the HPV vaccine, which prevents virus-induced cancers.

Therapeutic Vaccines: Aim to stimulate an immune response against existing tumours by introducing tumour antigens.

4. Cytokine Therapy:

Interleukins and Interferons: Enhance the proliferation and activation of immune cells.

5. Monoclonal Antibodies:

Targeted therapy involves using monoclonal antibodies that can be designed to target specific antigens on cancer cells, marking them for destruction or delivering cytotoxic agents directly to the tumour.

The immune system's ability to detect and eliminate cancer is complex and involves a coordinated effort between innate and adaptive immunity. Advances in understanding these mechanisms have led to significant developments in cancer immunotherapy, offering new hope for effective cancer treatment.

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