susceptible to chemically-induced, as well as spontaneous, tumors. Shankaran, V. et al. IFN and lymphocytes prevent primary tumor development and shape tumor immunogenicity. Nature , 410, 1107–1111 (2001)
Pham SM, 1995. Ann. Thorac.Surg. 60:1623–26
608 cardiac transplant patients at the University of Pittsburgh between 1980 and 1993, the prevalence of lung tumors was 25-fold higher than in the general population .
(A) Age- and sex-matched mice were inoculated with 100 ug MCA and monitored for tumor development for 160 days.
(B) Mice housed in a specific pathogen-free facility were monitored for spontaneous tumor development between 13–24 months.
(C) Infiltrating lymphocytes correlate with the favorable clinical prognosis (ovarian, colon).
(d) Adoptive transfer of tumor specific T cells suppresses tumor growth.
肿瘤免疫学基础 和研究进展
刘永忠
上海市肿瘤研究所 癌基因和相关基因国家重点实验室
Email：liuyzg@
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Carcinogenesis and immune microenvironments
Adult cells / progenitor cells
Stress signals (virus, injury, metabolism deficiencies, etc )
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Immunosuppressed transplant recipients have higher incidences of cancers
Birkeland SA(1995. Int. J. Cancer 60:183–89)
5692 renal transplant patients from 1964–1982 howed increased standardized cancer incidence ratios for colon, lung, bladder, kidney, ureter, and endocrine tumors compared to the general population.
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CANCER IMMUNOSURVEILLANCE IN HUMANS
(a)Immunosuppressed transplant recipients display higher incidences of cancers.
(b) Cancer patients can develop spontaneous adaptive and innate immune responses to the tumors.
CANCER IMMUNOSURVEILLANCE Milestone 3, NATURE 2006
1909 : “Thanks to the immune system, tumor development was usually suppressed.”
Thomas L. 1959. Discussion. In Cellular and Humoral Aspects of the Hypersensitive States, ed. HS Lawrence, pp. 529–32.New York: Hoeber-Harper
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Evidence for Hematopoietic immune system as anti-carcinogenic force
MOUSE MODELS Deletion of immune cells favors tumor growth, ablation of cytokine IFN, STAT1, etc, blockage of TGF, preventional or therapeutic Vaccination work in certain cancer models.
Pre-malignant / being transformed
Cancer cells
OIS, OIA,
Quiescence
Non-Parenchymal Cells
Tumor metastasis/progression
讨论要点
1. 免疫编辑 2. 肿瘤免疫微环境形成的细胞和分子 3.细胞死亡或衰老和肿瘤免疫反应
Burnet FM. 1970. The concept of immunological surveillance. Prog. Exp. Tumor Res. 13:1–27
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Robert Schreiber, in 2001, found that immunodeficient mice are m IMMUNOEDITING）
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CANCER IMMUNOSURVEILLANCE（肿瘤免疫监视） Historical Perspective
Paul Ehrlich
(The Nobel Prize in Physiology or Medicine 1908)