肿瘤免疫的概念起源（ZZ from DXY）

饶冠华

肿瘤免疫的概念起源于本世纪初。1909年Ehrlich首先提出，免疫系统不仅负责防御微生物侵犯，而且能从肌体内清除改变了的宿主成分。此后人们认识到癌细胞是改变了的宿主成分。本世纪中期，Foley证实，纯系小鼠诱发的肿瘤能在同系小鼠之间移植，如在肿瘤的生长过程中将移植瘤完全切除，小鼠会对再次接种的肿瘤产生抵抗能力，再次接种的肿瘤或者不再生长，或者长到一定的大小便自行消退。这种抗性有专一性，因为它对再次接种来源于同系动物的另一肿瘤没有抵抗能力。实验说明，肿瘤确能被宿主视为"非己"而产生特异的免疫排斥反应。这使人们相信机体存在着抗肿瘤免疫机制。六十年代经Thomas、Burnet和Good等人将该观点系统化，提出了免疫监视学说。免疫监视学说的中心思想是：免疫系统具有一个十分完备的监视功能，能精确地分?quot;自己"和"非己"的成分；它不仅能清除外界侵入的各种微生物，排斥同种异体移植物，而且还能消灭机体内突变的细胞，防止肿瘤的生长，保护机体的健康。每当免疫监视功能由于这种或那种原因被削弱时，便为肿瘤的发生提供了有利条件；如果机体不具备免疫监视功能，人类的肿瘤发病率会大大提高。 临床也得到了一些支持的证据。但是目前仍然存在争论。& [' Y3 o- X$ a
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1）Burnet FM.
) Q  k9 e# ?; u2 L1 `' {/ Y2 KThe concept of immunological surveillance.' H$ _  r% r6 Z; G
Prog Exp Tumor Res. 1970;13:1-27. Review. .
; {) j2 p! L! DPMID: 4921480 [PubMed - indexed for MEDLINE] ( l" @, C/ D* @9 Y2 ]2 f
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2）Burnet FM. Related Articles, Links ; Q2 W+ ^! z8 W) p' Q
Immunological surveillance in neoplasia.
8 ~9 n% x( s# y2 V% \( J3 I% x1 zTransplant Rev. 1971;7:3-25. , a! H! C4 N4 S# |* h& [1 a. I
PMID: 5146537 [PubMed - indexed for MEDLINE] 8 z( v6 L: `2 j* G2 a9 _7 e# R" N7 m

9 `3 Z- a. U) _" n6 {2 S8 P目前关于免疫监视学说的进展和改进( [( y% H7 L2 O" Z2 D1 m

  w) E7 {6 F. u, _, a1）Klein G, Klein E. 1 B* D! `' u  Z; L
Surveillance against tumors--is it mainly immunological?1 z! e! ?0 b) i- g# H
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2）Zitvogel L, Tesniere A, Kroemer G.
. D/ [3 K" [  ~* O9 oCancer despite immunosurveillance: immunoselection and immunosubversion.
' j$ Q& P& B9 w! k. aNat Rev Immunol. 2006 Oct;6(10):715-27. Epub 2006 Sep 15. Review. , H, e& t" Z. n: g- E
PMID: 16977338 [PubMed - indexed for MEDLINE] 3 U2 E/ \' h: Z3 k6 k/ M( m

; C; o0 {9 X, Q0 K: u: j3）Smyth MJ, Dunn GP, Schreiber RD.
2 Q+ c0 t* ^) J! g9 zCancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity.$ h* x- h9 m. U. i% W8 T3 C2 K: C+ B
Adv Immunol. 2006;90:1-50.
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. Z/ {% i( h; r1 d: j4）Ichim CV. ' k( a6 S4 `' [/ x
Revisiting immunosurveillance and immunostimulation: Implications for cancer immunotherapy.
- f# I% k! J3 m! XJ Transl Med. 2005 Feb 8;3(1):8. 8 b6 H7 h7 j7 i6 Y8 a( s
PMID: 15698481 [PubMed - as supplied by publisher]
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% J; @# i$ ]" ~7 Q# Y  |5）Dunn GP, Old LJ, Schreiber RD.
* M7 U4 R/ u2 i+ t. ?The immunobiology of cancer immunosurveillance and immunoediting.
7 D" I# m5 X. g( D. J/ cImmunity. 2004 Aug;21(2):137-48. Review.
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6） Qin Z, Blankenstein T.
% k0 v4 L3 n: F# S" vA cancer immunosurveillance controversy.2 ?2 h* L% b& y0 }6 q; ?
Nat Immunol. 2004 Jan;5(1):3-4; author reply 4-5. No abstract available.
7 [! F" J' N  w+ Q9 z& d* D: YPMID: 14699396 [PubMed - indexed for MEDLINE]
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: }& J6 s0 y: _7 r( Y9 o6 I7） Boon T, van Baren N. 6 Y' m, q6 b* S; g' O3 U
Immunosurveillance against cancer and immunotherapy--synergy or antagonism?
' L3 f. y' |; D0 p- ?9 GN Engl J Med. 2003 Jan 16;348(3):252-4. 8 w: T0 G5 t+ M) k+ X' ^/ i
PMID: 12529468 [PubMed - indexed for MEDLINE] 3 g1 {' M9 x: [( `
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8: Ochsenbein AF. + N2 l* @0 y( F9 I
Principles of tumor immunosurveillance and implications for immunotherapy.
* O" B8 Q4 K& v0 ECancer Gene Ther. 2002 Dec;9(12):1043-55. Review. 5 ^# n+ T. s' v( j* N; O* @
PMID: 12522443 [PubMed - indexed for MEDLINE] . \. [+ [+ ~+ o
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9: Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD.
2 A( V& i/ |& H9 BCancer immunoediting: from immunosurveillance to tumor escape.1 l) M- Z- l5 X$ t! A
Nat Immunol. 2002 Nov;3(11):991-8. Review.
6 `$ d" D# l! p& T; E1 x# ~; xPMID: 12407406 [PubMed - indexed for MEDLINE] ' ^$ I4 O$ x" Z
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10）Lanier LL.   P: v% S' g. F$ U3 T: X' b, y
A renaissance for the tumor immunosurveillance hypothesis.7 S; @, u2 ]) I! p. x% q2 X8 G
Nat Med. 2001 Nov;7(11):1178-80. / M9 u5 e6 u1 S5 Z
PMID: 11689875 [PubMed - indexed for MEDLINE]
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9 a2 y3 f) ^6 u  Y2 {/ _* e) r' O$ J著名的肿瘤免疫学奠基人之一Richmond T. Prehn首先发现肿瘤特异性抗原，在1970年左右提出肿瘤免疫刺激学说，与诺贝尔奖获得者Bernet的免疫监视学说相反。' v7 h% N/ V1 W% s# w$ x

! I  b: \2 L5 V% n. j3 v1）Prehn RT, Lappe MA.
5 m: h% x1 }+ B: ^6 aAn immunostimulation theory of tumor development.9 n- S) P* p3 D9 ?1 h' N# y
Transplant Rev. 1971;7:26-54. Review. 5 @0 r- ^& Q5 ~
PMID: 4947774 [PubMed - indexed for MEDLINE]
8 Y4 f( ~7 u. t1 n2） Prehn RT. & h8 [- W/ {  w
Immunosurveillance, regeneration and oncogenesis.
2 F( s9 p! a2 r1 G. O' j) P8 h% sProg Exp Tumor Res. 1971;14:1-24. Review. . 6 G# p& ?, C4 g5 O
PMID: 4944395 [PubMed - indexed for MEDLINE]
/ c" @  B( Q3 z: H8 H3）Prehn RT, Prehn LM.
( R. D) x6 I0 S( k7 PThe autoimmune nature of cancer.
9 S6 d# k) J( Y9 j* i+ E4 TCancer Res. 1987 Feb 15;47(4):927-32. Review.
$ o5 X  c& C2 O$ BPMID: 3542202 [PubMed - indexed for MEDLINE] 7 M+ y: H; ?( I  f4 q) Y
4）Prehn RT, Prehn LM. . n1 `, \+ l# N9 n2 L/ B; T
Immunostimulation of cancer versus immunosurveillance.
% [/ z# \9 y. {Medicina (B Aires). 1996;56 Suppl 1:65-73. Review. & t$ D* F  |/ }  [. z
PMID: 9224976 [PubMed - indexed for MEDLINE]
& T; `8 P/ c6 G4 w+ _9 }) ?% a5） Prehn RT.
$ M! h" J) r9 q7 ]* V7 H" z+ LStimulatory effects of immune reactions upon the growths of untransplanted tumors.2 e" H& z* Q: ?
Cancer Res. 1994 Feb 15;54(4):908-14. Review.   `7 v- S1 O9 [
PMID: 8313380 [PubMed - indexed for MEDLINE] : k. {) z; n- o5 j: r  h# X+ h7 P
6）Prehn RT. 0 b5 R4 A. i. x: ~' h( n6 Q
An adaptive immune reaction may be necessary for cancer development.% F" q- W# a& l) }! r* z
Theor Biol Med Model. 2006 Feb 3;3(1):6 [Epub ahead of print] " A$ r8 h" W' `2 S# W+ p+ Q
PMID: 16457723 [PubMed - as supplied by publisher]

anql

好地方一定常来支持

饶冠华

1909年 Immune surveillance 免疫监视
- z" [( m/ r' U* A免疫系统有惊人的能力来检测出外源物质，而保留自身。Paul Ehrlich深信癌细胞中，突变累积和改变的基因扩模式也能使免疫系统像清除炎症物质那样破坏癌细胞，并于1909年提出免疫系统可以抑制肿瘤的发展。但是试图开展的免疫治疗却没有得到Ehrlich设想的那样成功。在1957年，Richmond Prehn 和Joan Main证实并得出结论肿瘤免疫只对化学致癌物引起的肿瘤起作用，对自发产生的肿瘤却无效。从此，开始了这方面的大量研究。Harold Hewitt及其同事对这些研究做了总结认为自发性肿瘤是非免疫源的。此外，Osias Sutman在1974年的报道提出在化学致癌物引起的肿瘤中免疫监视有效是不正确的。然而，Aline van Pel和Thierry Boon发现预防接种可以引起肿瘤特异性免疫反应，这使肿瘤免疫的研究得到了重新振作，但是他们没有得到有效的免疫反应。Pierre van der Bruggen从技术上得到了突破，并证实肿瘤抗原能激发肿瘤特异性免疫反应。
( u2 i- |  Q& F$ ~: Y2001年，Robert Schreiber重新开始了免疫监视的研究，认为免疫系统对肿瘤细胞产生了一个选择压力或者免疫编辑，造成免疫源的减少最终逃离免疫介导的根除。最近，Gerald Willimsky和Thomas Blankenstein提出在老鼠中散发性肿瘤不是失去了免疫源性，而是产生免疫耐受逃离了免疫根除，但是，和肿瘤生长相关的模式仍旧没有明确。+ t5 q& q6 B' A/ P( P
然而，Ehrlich的设想仍旧鼓舞着肿瘤免疫领域的研究，特别是对作为肿瘤治疗中一个有潜力的免疫治疗领域。

xiaodongqin

很好

花瓣雨

这个假说现在还流行吗

饶冠华

5# 花瓣雨
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现在还是有很多证据支持这个假说的
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1: Front Biosci. 2009 Jan 1;14:167-76. - G$ v5 J: n0 R0 h0 s0 V
Tumorigenesis and anti-tumor immune responses in Xenopus.
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: g1 g0 h3 D! ^3 J& y$ _+ e! GGoyos A, Robert J.& p+ G* s5 b4 ^
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.: O. U/ Z* Y7 w' A5 m" n( [- F
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Despite intense study, the role of the immune system in detecting (immunosurveillance), controlling and remodeling (immunoediting) neoplasia remains elusive. We present here a comparative view of the complex interactions between neoplasia and the host immune system. We provide evidence, in the amphibian Xenopus laevis, consistent with an evolutionarily conserved and crucial role of the immune system in controlling neoplasia, which involves a striking variety of anti-tumoral immune effectors including conventional CTLs, classical MHC class Ia unrestricted CTLs (CCU-CTLs) that interact with nonclassical MHC class Ib molecules, CD8 NKT-like cells and NK cells. We also review the tumors found in X. laevis with an emphasis on thymic lymphoid tumors and a rare ovarian dysgerminoma. Finally, we consider the use of X. laevis for in vivo study of tumorigenesis. Given our current knowledge, the experimental systems already established in X. laevis, and the rapid accumulation of genetic resources for the sister species Silurana (Xenopus) tropicalis, it is our conviction that these species provide an ideal alternative to the murine system for studying tumorigenesis and tumor immunity.
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PMID: 19273061 [PubMed - in process]

饶冠华

1: Oncogene. 2008 Oct 6;27(45):5932-43. Links
3 X0 f: v1 I4 \& LNK cells and cancer immunosurveillance." q" I. T, P0 D- J: I: r% }, z/ c8 c

* A& o3 t$ L# l3 `3 oWaldhauer I, Steinle A.- [+ u9 |: R. G* K9 e/ A
Department of Immunology, Interfacultary Institute for Cell Biology, Eberhard Karls University of Tübingen, Tübingen, Germany.
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4 M; o3 U& L+ ?& C/ b0 r( vNatural killer (NK) cells are lymphocytes of the innate immune system that monitor cell surfaces of autologous cells for an aberrant expression of MHC class I molecules and cell stress markers. Since their first description more than 30 years ago, NK cells have been implicated in the immune defence against tumours. Here, we review the broadly accumulating evidence for a crucial contribution of NK cells to the immunosurveillance of tumours and the molecular mechanisms that allow NK cells to distinguish malignant from healthy cells. Particular emphasis is placed on the activating NK receptor NKG2D, which recognizes a variety of MHC class I-related molecules believed to act as 'immuno-alerters' on malignant cells, and on tumour-mediated counterstrategies promoting escape from NKG2D-mediated recognition.
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PMID: 18836474 [PubMed - indexed for MEDLINE]

饶冠华

1: Oncogene. 2008 Oct 6;27(45):5920-31.
$ ^' t5 i  n: vThe Janus face of dendritic cells in cancer.# M% @6 k5 N# M+ U# H  F
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Chaput N, Conforti R, Viaud S, Spatz A, Zitvogel L.' y+ c' C  R7 p: }8 M+ \
Institut Gustave Roussy (IGR), Villejuif, France.1 s1 e: [4 v9 a0 Z: O( H+ n* {

9 c0 O5 e- o- UOn the basis of experimental models and some human data, we can assume that tumor outgrowth results from the balance between immunosurveillance (the extrinsic tumor suppressor mechanisms) and immunosubversion dictated by transformed cells and/or the corrupted surrounding microenvironment. Cancer immunosurveillance relies mainly upon conventional lymphocytes exerting either lytic or secretory functions, whereas immunosubversion results from the activity of regulatory T or suppressor myeloid cells and soluble mediators. Although specific tools to target or ablate dendritic cells (DCs) became only recently available, accumulating evidence points to the critical role of the specialized DC system in dictating most of the conventional and regulatory functions of tumor-specific T lymphocytes. Although DC can be harnessed to silence tumor development, tumors in turn can exploit DC to evade immunity. Indeed, DCs harbor defects in their differentiation and stimulatory functions in cancer-bearing hosts and can actively promote T-cell tolerance to self-tumor antigens. In this review, we will focus on the dual role of DC during tumor progression and discuss pharmacoimmunological strategies to harness DC against cancer.

虚竹

谢谢版主的资料

wangabu

好贴，顶一下，谢了