TUMOR

IMMUNOLOGY
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• Tumor immunology is the study of the antigens associated
with tumors, the immune response to tumors, the tumor’s
defect on the host’s immune status, and the use of the
immune system to help eradicate the tumor.

• The ultimate goal of tumor immunology is to induce

clinically effective anti-tumor immune responses that
would discriminate between tumor cells and normal cells
in cancer patients.
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Normal cell growth and division are regulated processes

designed to rapidly produce new cells when necessary,
inhibit cell division when sufficient cells are present, and limit
life span.

Proto-oncogenes- these are regulatory genes that promote

cell division but can cause uninhibited activity if their
expression is altered or if they are mutated into oncogenes.

Similarly, mutations or malfunctions in tumor suppressor

genes that remove growth-inhibitory signals can cause
tumors.
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Therefore, tumors are composed of cells that possess

many of the attributes of the normal cells/tissues from
which they arose but have accelerated or dysregulated
growth.
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BENIGN TUMORS
-if a tumor grows incapsulated and does not invade healthy surrounding
tissue and normal body function is preserved and unchanged.

-are abnormal growth of cells that serve no purpose.

- are often surrounded by a protective “sac” – a mechanism performed by

your immune system – that segregates it from the rest of your body and
enables it to be easily removed.

- Overall, benign tumors respond well to treatment and the prognosis is

usually favorable.
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COMMON TYPES OF BENIGN TUMORS

•Adenomas (epithelial tissue that covers the organs and
glands)

•Meningiomas (brain and spinal cord)

•Fibromas or fibroids (connective tissue of any organ – most

commonly found in the uterus)

•Papillomas (skin, breast, cervix, and mucus membranes)

•Lipomas (fat cells)

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COMMON TYPES OF BENIGN TUMORS

•Myomas (muscle tissue)

•Hemangiomas (blood vessels and skin)

•Neuromas (nerves)

•Osteochondromas (bones)

•Nevi (moles)
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MALIGNANT TUMORS
-The word malignant is Latin for “badly born.” 

-This type of tumor has the ability to multiply uncontrollably, to

metastasize (spread) to various parts of the body, invade surrounding
tissue and greatly disrupt normal body functions.

-Malignant tumors are formed from abnormal cells that are highly
unstable and travel via the blood stream, circulatory system, and
lymphatic system. Malignant cells do not have chemical adhesion
molecules to anchor  them to the original growth site that benign tumors
possess.

-Malignant cells typically differ visually from normal cells, are

metabolically more active to support their growth, and express different
genes or different levels of gene products as compared to normal cells.
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COMMON TYPES OF MALIGNANT TUMORS

•Carcinomas- arising from epithelial tissue, such as glands, breast,

skin, and linings of the urogenital, digestive, and respiratory systems
(89.3% of all cancers)

•Sarcomas- solid tumors of muscles, bone, and cartilage that arise

from the embryological mesoderm (1.9% of all cancers)

•Lymphomas, Myelomas- diseases of the lymp nodes and spleen

that cause excessive production of lymphocytes (5.4% of cancers)

•Leukemias- disease of bone marrow causing excessive production

of leukocytes (3.4% of all cancers)
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BENIGN VS. MALIGNANT

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CARCINOGENS

•Radiation- ultraviolet light, sunshine; X-rays, radioactive

elements induce DNA damage and chromosome brakes.

•Chemical- smoke and tar, countless chemicals that damage

DNA (mutagens)

•Oncogenic viruses- insert DNA or cDNA copies of viral

oncogenes into the genome of host target cells.

•Hereditary- certain oncogenes are inheritable.

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The conversion of a normal cell to a malignant cell is typically a process,

not an event.

During the induction phase, cells are exposed to a variety of

environmental insults including chemical carcinogens, oncogenic viruses
and radiation. Cancer may develop as the result of multiple mutations
caused by these insults, and it more readily develops in cells genetically
predisposed to these mutations. During the induction phase, which may
take months to years, cells exhibit dysplasia or abnormal growth that is
not yet considered neoplasia, or consistent with a tumor.
STAGES OF CANCER
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THE TNM SYSTEM

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IMMUNOSURVEILLANCE

Immune surveillance is a natural physiologic function to

allow recognition and destruction of transformed cells
before they grow into tumors, and to kill tumors after they
are formed.

The immune surveillance theory states that the immune

system is constantly monitoring the body for the appearance
of tumor cells, and that the majority of these aberrant cells
are destroyed by the immune system before giving rise to
clinically manifest tumors
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IMMUNOSURVEILLANCE

1.Natural killer cells- are aggressive cells of the immune

system that play an important role in fighting cancer.

- are the "first responders" that are on the scene

before the T cells are summoned.

If a cell is not recognized as being a normal part of the body,

the NK cell can perform one of two function:
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IMMUNOSURVEILLANCE
•Cytotoxic (Cell Killing)
NK cells may be cytotoxic. In this process, the NK cell penetrates the
cell and releases toxic granules into the abnormal cells. These
granules then create holes in the cell membrane, allowing them to
swell and burst and killing the cell on contact. Instead of bursting,
the cell may instead be directed in a process of controlled death
called apoptosis.
•Immunoregulation
Natural killer cells may also be used as a form
of immunoregulation. In this process, the NK cells regulate the
function of the immune system by producing substances known
as cytokines. You can visualize cytokines as the "hormones of the
immune system" which stimulate other parts of the immune system.
It is these other parts of the immune system that, once stimulated,
result in the death of the cancer cell or viral-infected cell.
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IMMUNOSURVEILLANCE
2. Macrophages-
Macrophages can prevent the spread of cancer based on their activation
state. Activated macrophages can kill transformed cells more efficiently
than the normal cell. M1 cells especially treat the tumor cells like an
infectious organism and produces cytokine tumor necrosis factor (TNF) to
kill the tumor but M2 macrophages on the other hand are associated with
tumor progression.
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IMMUNOSURVEILLANCE
3. Cytokines- they are released in response to infection,
inflammation and immunity can function to inhibit cancer
development and progression. Alternatively, cancer cells can
respond to host-derived cytokines that promote growth, attenuate
apoptosis and facilitate invasion and metastasis.
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IMMUNOSURVEILLANCE

4. T lymphocytes-

The basis of adaptive tumor immunity is to destroy tumor cells by

CD8+ CTLs. Functioning of CD8+ cell requires cross presentation of
the tumor antigen by the dendritic cells. Although CD8+ CTLs have
a substantial role to play in killing the transformed clones but not
much is known about the efficacy of CD4+ helper T –cells in tumor
immunity.
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IMMUNOSURVEILLANCE
T lymphocytes-
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IMMUNOEDITING
Cancer immunoediting is the process by which immune system
components protect the host against primary tumor development
and/or enhance tumor escape either by sculpting tumor
immunogenicity or attenuating anti-tumor immune responses.

Immunoediting proposes to explain the complex evolution of the

“cat and mouse” relationship that exists between cancer cells and
the immune system during the development of an overt
malignancy.

Tumors tend to be genetically unstable; thus immune system can

kill and also induce changes in the tumor resulting in tumor escape
and recurrence.
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IMMUNOEDITING
Immunoediting has three temporally distinct stages, termed elimination,
equilibrium, and escape.

1. Elimination is equivalent to immune surveillance, in which innate

and adaptive components of the immune system act to eradicate
cancers that arise in the organism. 

2. Equilibrium in immunoediting is reached when the immune

system can still control tumors but no longer eradicate them. 

3. Immune Escape, in which tumor cells can defeat, evade, or

tolerate the immune system.
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IMMUNOEDITING
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IMMUNOEDITING
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TUMOR MARKERS

A Tumor marker is a biological substance synthesized and released

by:
•The tumor
•Or by the host in response to tumor tissue

It may be used to:

•Detect the presence of a tumor
•Monitor the progress of disease
•Monitor the response to treatment
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TUMOR MARKERS
How to identify tumor marker?

On cell
Immunocytochemistry, Flow cytometry

On tissue
Immunohistochemistry

In body fluids

Blood, urine, CSF, Amniotic fluid
RIA, EIA
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PRINCIPLES OF LAB TESTS FOR SCREENING,

DIAGNOSING, AND MANAGING TUMORS
Screening test
Tumor markers play a limited role for tumor screening, because
oRelatively low sensitivity
oLack of sensitivity
Inappropriate for the detection of small in situ cancer
However, successful cancer screening has been carried out by
measuring tumor markers
Eg. PSA – prostate cancer

Diagnostic tests- are those that help determine differential diagnosis,

tumor stage, prognosis, and therapy selection.

Disease prevalence profoundly impacts the test’s usefulness.

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TUMOR MARKERS IN CANCER

MANAGEMENT

Screening
Diagnosis
Staging and Prognosis
Therapy Monitoring
Detecting Recurrence
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TUMOR MARKERS IN CANCER

MANAGEMENT
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IDEAL TUMOR MARKER CHARACTERISTICS

Sensitive and Specific

Presence of a given marker identifies an exact malignancy
Concentration proportional to tumor size
Concentration changes with growth or reduction
malignancy
Concentration is a good indicator of prognosis
Short half-life (concentration reflects current conditions)
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REALITY OF TUMOR MARKERS

Unfortunately, most tumor markers only possess some of the

ideal characteristics (never all of them)

Most tumor markers are not very sensitive and are poor
screening test for the detection of malignancies

Most tumor markers are best utilized to confirm or monitor

already diagnosed cancers
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TUMOR ANTIGENS
Tumor antigens are useful tumor markers in identifying tumor cells
with diagnostic tests and are potential candidates for use in cancer
therapy.
Tumor specific antigens
•Direct product of oncogenesis
•Disorganization of the genetic information leading to synthesis of
antigens that are unique to the specific tumor cell
•(E.g. abnormal products of ras and p53 genes)

Tumor-associated antigens
Tumor-associated antigens (TAA) are antigens present in the tumor tissue
in higher amounts than in normal tissue. Most antigens are not specific
for individual tumors but rather are usually
Associated with different tumors.
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TUMOR-ASSOCIATED ANTIGENS

TUMOR MARKER EXAMPLES DISEASE ASSOCIATION

CLASS

Cell surface markers Estrogen/progesterone Prognosis for hormone

receptors therapy in breast cancer

CD markers on white blood Clonality and lineage of white

cells blood cell neoplasm
Proteins Thyroglobulin (TG) Well-differentiated papillary or
follicular thyroid carcinoma

Immunoglobulins (Ig) and Ig Multiple myeloma and

light chains (Bence Jones lymphoid malignancies
proteins)
Oncofetal antigens Alpha-1-fetoprotein (AFP) Germ cell carcinoma,
hepatocellular carcinoma

Carcinoembryonic antigen Colorectal carcinoma and

(CEA) some others
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TUMOR-ASSOCIATED ANTIGENS

TUMOR MARKER EXAMPLES DISEASE ASSOCIATION

CLASS

Carbohydrate antigens CA 125 Ovarian cancer

CA 15-3 Breast cancer

Blood group antigens CA 19-9 (related to Lewis Pancreatic and gastrointestinal
antigens) cancers
Enzymes/isoenzymes Prostate-specific antigen Prostate cancer
(PSA)

Alkaline phosphatase (ALKP) Bone and liver cancer

Neuron specific enolase Neutral tissue neoplasm

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TUMOR-ASSOCIATED ANTIGENS

TUMOR MARKER EXAMPLES DISEASE ASSOCIATION

CLASS
Hormones Human chorionic Germ cell carcinoma,
gonadotropin (HCG) trophoblastic tumors

Calcitonin Medullary thyroid cancer

Gastrin Pancreatic gastrinoma

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Tumor Markers Useful for Cancer Screening

Professional Consensus Recommendations
CANCER TYPE MARKER ADJUNCT TEST POPULATION
RECOMMENDED
Prostate Prostate-specific Digital rectal exam Men over 50 and with
antigen (PSA total at least 10 years of life
and free) expectancy

Colorectal Fecal occult blood Genetic testing Subjects over 50 years

old for occult blood;
genetic testing in
high-risk subjects
Liver Alpha-1-fetoprotein Ultrasound High-risks subjects
(AFP)

Ovarian Carbohydrate antigen Ultrasound Subjects with family

125 (CA 125) history of ovarian
cancer
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IMMUNOTHERAPY

Immunotherapy, also called biologic therapy, is a type of cancer

treatment that boosts the body's natural defenses to fight cancer.
It uses substances made by the body or in a laboratory to improve
or restore immune system function. Immunotherapy may work by:

•Stopping or slowing the growth of cancer cells

•Stopping cancer from spreading to other parts of the body

•Helping the immune system work better at destroying cancer

cells
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IMMUNOTHERAPY
•Cancer vaccines
A cancer vaccine is another method used to help the body fight disease. A
vaccine exposes the immune system to an antigen. This triggers the
immune system to recognize and destroy that antigen or related materials.

•T-cell therapy
T cells are immune cells that fight infection. In T-cell therapy, some T cells
are removed from a patient’s blood. Then, the cells are changed in a
laboratory so they have specific proteins called receptors. The receptors
allow those T cells to recognize the cancer cells. The changed T cells are
grown in the laboratory and returned to the patient’s body. Once there,
they seek out and destroy cancer cells. This type of therapy is called
chimeric antigen receptor (CAR) T-cell therapy.

The use of T cells for CAR therapy has been very effective in treating certain
blood cancers.
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IMMUNOTHERAPY
•Oncolytic virus therapy
Oncolytic virus therapy uses genetically modified viruses to kill cancer cells.
First, the doctor injects a virus into the tumor. The virus then enters the
cancer cells and makes copies of itself. As a result, the cells burst and die. As
the cells die, they release specific substances called antigens. This triggers the
patient’s immune system to target all the cancer cells in the body that have
those same antigens. The virus does not enter healthy cells.
•T-cell therapy
T cells are immune cells that fight infection. In T-cell therapy, some T cells are
removed from a patient’s blood. Then, the cells are changed in a laboratory
so they have specific proteins called receptors. The receptors allow those T
cells to recognize the cancer cells. The changed T cells are grown in the
laboratory and returned to the patient’s body. Once there, they seek out and
destroy cancer cells. This type of therapy is called chimeric antigen receptor
(CAR) T-cell therapy.
The use of T cells for CAR therapy has been very effective in treating certain
blood cancers.
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IMMUNOTHERAPY
•Non-specific immunotherapies
Like monoclonal antibodies, non-specific immunotherapies also help the
immune system destroy cancer cells. Most non-specific immunotherapies
are given after or at the same time as other cancer treatments, such as
chemotherapy or radiation therapy.

•Checkpoint inhibitors 
Which are drugs that help the immune system respond more strongly to a
tumor. These drugs work by releasing “brakes” that keep T cells (a type
of white blood cell and part of the immune system) from killing cancer
cells. These drugs do not target the tumor directly. Instead, they interfere
with the ability of cancer cells to avoid immune system attack .
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CANCER KEYPOINTS (WHO)

•Cancer is the second leading cause of death globally, and is

responsible for an estimated 9.6 million deaths in 2018. Globally,
about 1 in 6 deaths is due to cancer.

•Around one third of deaths from cancer are due to the 5 leading
behavioral and dietary risks: high body mass index, low fruit and
vegetable intake, lack of physical activity, tobacco use, and alcohol
use.

•Tobacco use is the most important risk factor for cancer and is
responsible for approximately 22% of cancer deaths.
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Thank you!

Prepared by: Jenny M. David, RMT