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.
Lim ju
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