TUMOR IMMUNOLOGY

Jan eromski
2011/2012

EVIDENCE FOR ANTI-TUMOR

IMMUNOLOGICAL REACTIVITY

Lymphoid cell infiltrates and proliferative

reaction in regional lymph nodes correlate
with favourable prognosis in some tumors,
Transplants of experimental tumors are
rejected in animals previously exposed to
the same tumor,

EVIDENCE FOR ANTI-TUMOR

IMMUNOLOGICAL REACTIVITY-2

This resistance may be transfered to another

animal by means of lymphocytes of animal
previously harboring or exposed to this
tumor,
Individuals with immunodeficiencies show
higher frequencies of some tumor types

IMMUNOLOGICAL SURVEILLANCE
Definition
prevention of development of the majority
of tumors by early destruction of atypic
cells by the immune system of the host.
Evidence
spontaneous regression of cancer, higher
incidence of tumors in early childhood and
in elderly people, autopsy findings.

TUMOR ANTIGENS

Tumor specific antigens (TSA) : expressed only

on tumor cells and not on normal ones
Tumor associated antigens (TAA)- may be
expressed in variable amounts also on normal cells

TUMOR ANTIGENS-2
In terms of origin the following TAA are

distinguished:
Ag of spontaneous tumors of unknown etiology
Ag of tumors induced by oncogenic viruses
Ag carcino-embryonic (oncofetal ones)
Ag of tumors induced by chemicals and/or
radiation

TYPES OF TUMOR ANTIGENS RECOGNISED

BY T CELLS

VIRUSES AND HUMAN TUMORS

Primary liver cancer: HBV, HCV
Cervical cancer: HPV 16, 18 and other
Burkitt lymphoma and other lymphomas: EBV
Nasopharyngeal carcinoma: EBV: HTLV-1
Adult T cell leukaemia: (HTLV-1)
Kaposi sarcoma: herpes virus-8 (KSHV)

ONCO-FETAL ANTIGENS
Features: not expressed in healthy people
in postnatal life but may abundant in fetal
period. They are encoded in geno
Their expression is the result of
derepression of particular gene.

ONCO-FETAL ANTIGENS-2
Carcinoembryonic antigen (CEA): cell
membrane glycoprotein (200 kDa) of many
human cancers
-fetoprotein (fetal albumin) major fetal
serum protein. Present in cells of primary
hepatic carcinoma and in malignant
germinal teratomas
PSA prostate specific antigen

IMMUNOLOGICAL FACTORS
OF ANTI-TUMOR RESPONSE
Antibodies
Cytotoxic T lymphocytes - CTL (CD8+)
Cytokines with cytotoxic properties
(TNF-alfa, LT)
Immunoregulatory cytokines (IFN-gamma,
IL-2, IL-12, IL-18)
NK cells, NKT cells, gamma/delta T cells
Macrophages, granulocytes - ADCC

TUMOR ESCAPE MECHANISMS

Tumors progression and growth are faster than

the generation of the immune response (sneaking
through mechanism)
Tumor and its microenvironment inactivate most
of the host defense mechanisms

HLA I

CD44 v6

TUMOR CELL COUNTER ATTACK

MALIGNANT PLEURAL EFFUSIONS

SURFACE EXPRESSION OF Fas AND
FasL ON TUMOR CELLS

TUMOR EVASION OF
HOST IMMUNE
RESPONSE

IMMUNOTHERAPY
OF CANCER

TUMOR IMMUNOTHERAPYPOSSIBILITIES

Monoclonal antibodies
Sensitized T (CD8+) cells
LAK cells (lymphokine activated killers)
Cytokines or their genes (IL-2, IL-12, IFNalfa etc.)

TUMOR IMMUNOTHERAPYPOSSIBILITIES -2
NK cells
Co-stimulatory molecules or their genes
inserted into tumor cells
Dendritic cells loaded with tumor peptides
Nonspecific immunotherapy (BCG)

Monoclonal Antibodies used in

Cancer Therapy
Campath 1H [CD52] - CLL
Rituximab [CD20] - as above
Epratuzumab [CD22] - as above
IDEC-152 [CD23] - as above
Cetuximab [EGFR] - colon, HNC
MDX-447 [EGFR i CD64]- as above
Gefitinib
[EGFR-TK] - prostate, lung cancer
Herceptin
[EGFR] - mammary cancer

Gene Gun

Tumor microenvironment.
Evaluation of fine needle aspiration biopsy
by means of DNA microarray