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Xue-Feng Bai, MD, Ph.D. Division of Cancer Immunology Department of Pathology The Ohio State University Email: Xue-Feng.Bai@osumc.edu
Reference
The basic science of oncology
Chapter 20: Cancer and immune system Chapter 21: Biological therapy of cancer
Important features of the immune system Innate immunity & adaptive immunity Response to foreign antigens Self tolerance Immunological memory
MHC molecules
Figure 5-11
MHC polymorphism
Figure 5-13
Figure 5-17
Does immune system play a role in the control of cancer? Increased cancer incidence in immuno-compromised patients. Occasional spontaneous regressions of cancers in immunocompetent hosts.
Immunotherapy of cancer
Passive immunotherapy: Antibodies (standard therapy in certain cancer) cytokines (e.g. IL2/IL15, IFN-alpha) Cells (Adoptive transfer of autologous T cells) Active immunotherapy: Allogeneic bone marrow transplantation (GVH) Specific tumor vaccines (i.e. peptides, idiotype vaccine etc) Assisted antigen presentation (DC)
ADCC
Induction of apoptosis
Dudley ME, et al: Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850-854.
IFN-alpha: 90% hairy cell leukemia IL-2: Renal cell carcinoma, melanoma IL-15: ?
Cancer vaccination
DNA vaccination
Nature Medicine 10, 909 - 915 (2004) Cancer immunotherapy: moving beyond current vaccines Steven A Rosenberg, James C Yang & Nicholas P Restifo Great progress has been made in the field of tumor immunology in the past decade, but optimism about the clinical application of currently available cancer vaccine approaches is based more on surrogate endpoints than on clinical tumor regression. In our cancer vaccine trials of 440 patients, the objective response rate was low (2.6%), and comparable to the results obtained by others. We consider here results in cancer vaccine trials and highlight alternate strategies that mediate cancer regression in preclinical and clinical models.
1. Self-tolerance 2. Suppressor cells Myeloid suppressor cells (MSC) Granulocyte suppressors (GS) TR (CD4+CD25+) Ts: Qa-1-restricted Tr1: TGF- producer (class II-restricted) Th3: IL-10 producer (class II-restricted) NKT: (CD1d-restricted) IL-13 producer 3. Immune evasion
6. Tumors and/or their surrounding stroma may produce immunosuppressive factors such as TGF- (Singh et al, J Exp Med 175:139-146, 1992) 7. Expression of FasL on tumor cells can induce apoptosis of T cells entering the site of tumor growth (OConnell et al, J Exp Med 184:1075-82, 1996;
Strand et al, Nature Med 2:1361-70, 1996; Hahne et al, Science 274:1363-1366, 1996; Andreola et al, J Exp Med 195:1303-1316, 2002)