CANCER IMMUNOLOGY

CANCER IMMUNOLOGY

Completed in two steps

 Immunosurveillance
 Immunoediting
 Immunosurveillance

Cells of immune system act as guard cells to recognize and eliminate continuously arising transformed cells
 Immunoediting 

Editing of tumor cells by immune system of individual

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IMMUNOEDITING

 Immunoediting is characterized by changes in the immunogenicity of tumors due to the anti-tumor response of the
immune system, resulting in the emergence of immune-resistant variants.
 Editing of tumor cells by immune system of individual
 It describes the relation between the tumor cells and the immune system. It is made up of three phases
  Elimination
 Equilibrium
 Escape.

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 ELIMINATION
The elimination phase, includes
 innate
 adaptive immune responses to tumor cells.

 For the immune response, several effector cells such as natural killer cells and T cells are activated by
the inflammatory cytokines, which are released by the growing tumor cells, macrophages and stromal
cells surrounding the tumor cells.
 These NK cells and macrophages produce cytokines (interleukin 12 and interferon gamma, which kill
tumor cells by cytotoxic mechanisms such as perforin, TNF-related apoptosis-inducing ligands
(TRAILs), and reactive oxygen metabolites. 
 Most of the tumor cells are destroyed in this phase, but some of them survive and leads to adaptive or
specific immune response (B and T cell responses) and again survivors reach to equilibrium phase.

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CONTI…………..

 Elimination phase is divided into

 Phase I
 Phase II
 Phase III
 Phase IV
CONTI………………..

Phase 1
 The first phase involves the initiation of an antitumor immune response. Cells of the innate
immune system recognize the presence of a growing tumor which has undergone mutation,
causing local tissue damage.
 This is followed by the induction of inflammatory signals which is essential for recruiting cells of
the innate immune system (e.g. natural killer cells, macrophages and dendritic cells) to the tumor
site.
 During this phase, the infiltrating lymphocytes such as the natural killer cells and natural killer T
cells are stimulated to produce INF-gamma.

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 Recognition of
tumor cells by
innate immune
response

Induction of
inflammatory
cytokines by
tumor cells

Phase I Attract NK cells,

Macrophages and
dendritic cells to
tumor site

These NK cells
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produce cytokine 7
(INF-gamma)
CONTI………………..

Phase II
 In the second phase, newly synthesized IFN-gamma induces tumor death (to a limited amount) as well as
promoting the production of chemokines (CXCL10, CXCL9 and CXCL11).
 These chemokines play an important role in promoting tumor death by blocking the formation of new
blood vessels. Tumor cell debris produced as a result of tumor death is then ingested by dendritic cells,
followed by the migration of these dendritic cells to the draining lymph nodes.
 The recruitment of more immune cells also occurs and is mediated by the chemokines produced during the
inflammatory process.
 Phase II

INF- gamma induce cell Promote the production of

death (to a limited extent) chemokines

Chemokines induce cell

Ingestion of debris by
death (by blocking formation
dendritic cells
of new blood vessels)

Ingestion of cell debris

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lymph nodes
CONTI………………

Phase III
 In the third phase, natural killer cells and macrophages transactivate one another via the reciprocal production of
IFN-gamma and IL-12.
 This again promotes more tumor killing by these cells via apoptosis and the production of reactive oxygen and
nitrogen intermediates.
 In the draining lymph nodes, tumor-specific dendritic cells trigger the differentiation of Th1 cells which in turn
facilitates the development of cytotoxic CD8+ T cells also known as killer T-cells.
 Phase III (take place at two sites)

Tumor site Regional Lymph nodes

NK cells and
macrophages transactivate Trigger the differentiation
each other via of T cell (first Th cells)

Th cells further activates

More killing of tumor cells
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Tc Cells 11
CONTI………………

Phase IV
 In the final phase, tumor-specific CD4+ and CD8+ T cells home to the tumor site
 The cytotoxic T lymphocytes then destroy the antigen-bearing tumor cells which remain at the site. destroy the
antigen-bearing tumor cells which remain at the site.
 destroy the antigen-bearing tumor cells which remain at the site.
 Phase IV

tumor-
specific CD4+ and
CD8+ T cells

destroy the antigen-

bearing tumor cells
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which remain at the site.
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EQUILIBRIUM

 The next step in cancer immuno editing is the equilibrium phase, during which tumor cells that have escaped
the elimination phase and have a non-immunogenic phenotype are selected for growth.
 Lymphocytes and INF-gamma exert a selection pressure on tumor cells which are genetically unstable and rapidly
mutating.
 Tumor cell variants which have acquired resistance to elimination then enter the escape phase. It is the longest of
the three processes in cancer immunoediting and may occur over a period of many years.
ESCAPE

 In the escape phase, tumor cells continue to grow and expand in an uncontrolled manner and may eventually lead
to malignancies.