Transcript TUMOR CELL RECEPTORS

TUMOR IMMUNOLOGY
Jan Żeromski
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:
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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
Tumor’s 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
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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