many genetic and environmental factors
can cause tumors to form for instance UV
radiation from the Sun can damage DNA
and other structures in melanocytes
which are the pigment producing cells in
the skin chronic damage to melanocytes
by UV radiation leads to most cases of
melanoma which is a type of skin cancer
as melanomas grow they can eventually
spread to other sites in the body such
as the lungs and liver the cells of the
immune system are continuously
monitoring our tissues natural killer
cells or NK cells sent stress associated
molecules on damaged and cancerous cells
dendritic cells or dcs activate
cytotoxic T cells which can then send
tumor associated antigens using their T
cell receptor and other Co receptors
once activated NK cells and cytotoxic T
cells release perforin and granzymes
these molecules punch holes in the
surface of the chima cells causing them
to die by apoptosis helper T cells
support these responses they help DC's
to activate cytotoxic T cells and they
produce cytokines such as interferon
gamma that recruit and activate more NK
cells as the tumor evolves genetic
changes occur that can give some tumor
cells a survival advantage this means
tumors are often heterogeneous for
instance tumor cells may no longer
express the molecules that are sensed by
the killer immune cells as the immune
system continues to kill the tumor cells
it can recognize the cells it can't
sense
more prevalent this is immuno editing it
leads to the emergence of a tumor that
can't be detected by the immune system
some tumor cells actively suppress
t-cells by expressing inhibitory
molecules such as PDL one PDL one binds
to the PD one receptor on t-cells and
deactivates them this is an immune
checkpoint in addition tumor cells can
attract immune cells that suppress the
activity of other immune cells thereby
supporting tumor growth these
immunosuppressive cells include
regulatory t-cells and certain types of
myeloid cells therefore the tumor
microenvironment is like the scene of a
battle between two opposing immune
responses one side of the immune system
is attacking the tumor while the other
side is helping it to grow scientists
are developing immunotherapies to help
strengthen the immune attack one
approaches adoptive t-cell transfer
cytotoxic t-cells taken from patients
with melanoma are selected for their
ability to attack tumor cells the best
killers are infused back into the
patient treating patients with cytokines
such as interleukin 2 and interferon
alpha can also boost the activity of
anti-tumor immune cells
an alternative approach is to target the
immune checkpoints for instance
antibodies that bind to PD one stop this
molecule from switching off cytotoxic T
cells another immune checkpoint being
targeted is ctla-4 blocking this
molecule helps DC's to drive anti tumour
t-cell responses not all patients will
respond to these immunotherapies and
some responses will be delayed combining
immunotherapies with chemotherapy or
radiotherapy can lead to a better
response in some patients
immunotherapies can themselves be
combined for example PD one and ctla-4
blockade can improve responses when
administered in combination activating
the immune system has risks some
patients develop harmful side effects
when their immune system attacks healthy
cells nevertheless there have been
encouraging results from clinical trials
this animation has focused on melanoma
but it's becoming clear that
immunotherapies can be used to treat
many different types of cancer
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