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immunology > tumor immunology > Flashcards

tumor immunology Flashcards

1
Q

Give 2 examples of virally induced tumor

what kind of antigen is it?

A

Virally induced：感染後會表現virus的特定抗原，產生突變的protein –> tumor specific antigen

  1. EBV virus 感染可能引發頭頸癌，表現出病毒特有的抗原
  2. HPVvirus 感染可能引發子宮頸癌
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2
Q

α fetal protein(AFP)

A

在人類肝癌病患的α fetal protein表現量會很多，在狗也有但case不多

Oncofetal tumor antigens：

在胚胎時期表現的蛋白質，在成熟的健康個體不會表現，若在出生後的個體驗到高量則可能與腫瘤發生有關

so it is a tumor associated antigen

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3
Q

CEA (Carcinoembryonic Antigen)

A

大腸癌指標, 在大腸癌及很多癌症所發現的一個抗原

  • Oncofetal tumor antigens：

在胚胎時期表現的蛋白質，在成熟的健康個體不會表現，若在出生後的個體驗到高量則可能與腫瘤發生有關

so it is a tumor associated antigen

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4
Q

the 3 most important transcription factor in tumor development

A

NF-Kb,STAT3,HIF1α

(activated in inflammatory cells, stromal cells, and tumor cells)

非常重要的transcription factor!

刺激腫瘤細胞生長、血管新生，也會促進chemokine、cytokines、 prostaglandins、COX2的分泌，強化發炎反應

跟腫瘤的形成有絕對、直接、強烈的關係

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5
Q

stat 3

A

Stat3：在tumor cell 中會過度表現，使腫瘤細胞不受控的生長

belong to Oncogene proteins: 本來是正常的 proteins，但在癌症裡由oncogene所產生，會被tumor cell 過度表現

非常重要的transcription factor (activated in inflammatory cells, stromal cells, and tumor cells) in promoting cancer!

刺激腫瘤細胞生長、血管新生，也會促進chemokines、cytokines、 prostaglandins、COX2的分泌，強化發炎反應

跟腫瘤的形成有絕對、直接、強烈的關係

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6
Q

selective cyclooxygenase 2 (COX2) inhibitors

A

drug, anti-inflammatory

reduce the opportunity of cancer incidence

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7
Q

HIF1α

A

Hypoxia inducible factor 1a

缺氧的組織所分泌，刺激血管內皮的新生

非常重要的transcription factor (activated in inflammatory cells, stromal cells, and tumor cells) in promoting cancer!

刺激腫瘤細胞生長、血管新生，也會促進chemokines、cytokines、 prostaglandins、COX2的分泌，強化發炎反應

跟腫瘤的形成有絕對、直接、強烈的關係

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8
Q

CSF

A

colonial stimulating factor

growth factor that 刺激血球細胞生長，讓更多granulocyte、monocyte產生

facilitate tumor microenvironment (by promoting chronic inflammation)

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9
Q

IL-10, IL-4、TGF-β

A

Released by tumor associated macrophage

協助macrophage 分化

-這些因子都是免疫抑制性的

不抑制Th1，因為Th1原本就對tumor反應弱，抑制Th2對tumor cell 最有利

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10
Q

Th17 and Treg

A

跟之前看到M1/M2的情況很相似，Th17和Treg之間也能互換！

  1. IL-6, TGF-β, IL-21 CD4+FOXP3+

à 有利Treg轉為Th17

  1. IL-2, RA (retinoicacid), IDO (indoleamine2,3-dioxygenase)

à 有利於Th17轉為Treg

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11
Q

Cancer Immunosurveillance

A

1957由Thomas and Burnet提出，免疫細胞會在身體各部組織間循環可以幫我們監控是否有不正常的細胞 (transformed cells)

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12
Q

Cancer immunoediting

A

Elinimination

開始腫瘤細胞有大量的抗原可以被免疫系統辨識，啟動先天與後天免疫清除腫瘤細胞

Equilibrium

低調風的腫瘤細胞(少量)不太表現抗原，也使免疫系統不太活化，經immune selection存活下來，雙方處在平衡狀態

Escape

創造了自己一套的免疫微環境：一邊逃避了adaptive immunity，一邊召喚innate immune cells來做自己的傭兵，腫瘤細胞大量生長伴隨慢性發炎，有M2、MDSC、Treg的產生協助腫瘤細胞生長，抑制免疫系統

Immunosurveillance 大、失、敗！

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13
Q

ＭＤＳＣ

A

Myeloid-derived suppressor cells

由bone marrow製造，是未成熟的monocytes and granulocytes，抑制免疫反應，當細胞缺氧的時候，會被召喚過來

ｆｕｎｃｔｉｏｎｓ

  1. 抑制抗腫瘤免疫反應(synthesis IL-10活化TAM抑制NK;IL-10&TGF-β維持Treg生長抑制T cell)

–> M1轉換成M2

TGF-β會抑制T cell、NK cell的活性

  1. 促進腫瘤侵襲和轉移by MMP、Chemokine
  2. IDO –>抑制dendritic cell(為教育T-cell的重要角色)
  3. 幫助angiogenesis和invasion
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14
Q

IDO

A

limit T-cell function and engage mechanisms of immune tolerance.

secreted by MDSC (recruited from bone marrow upon tissue hypoxia)

inhibit dendritic cell (which trains T cells)

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15
Q

how does T reg promotes cancer development?

A

1. competition：

－　effector T cell 競爭被DC活化的位置

－　CD25 (IL-2 receptor) –>　搶T-cell的IL-2

2. Targeting DCs：

表現很多CTLA-4，去競爭DC上的B7 family (CD80/86)，使Teff無法活化(因無法產生signal 2) 使DC不活化，使DC產生IDO抑制Teff

3. inhibitory cytokines:

分泌IL-10,IL-35,TGF-β抑制免疫反應

4. cytolysis:

透過granzime B, perforin 引發effector T cell的appotosis

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16
Q

PD-L1

A

存在正常組織細胞上，會bind在T cell上的PD-1上，trigger T cell的apoptosis，有剎車效應。可以用於抗癌藥的開發(PD-L1 blocker)或anti-PD-1(使T cell不被apoptosis)，使藥品與co-inhibitory surface molecules接合，使免疫細胞活性不被抑制

17
Q

CD73

A

To inhibit activation of immunity

CD73 is expressed by tumor cell as co-inhibitory surface molecules

hydrolase，用光ATP，使T cell沒有能量可以用！

18
Q
  1. 為什麼Ab沒辦法抑制tumor growth呢？
A
  1. 表面有補體活性抑制因子(C’-regulatory proteins)，抑制補體反應、MAC作用
  2. immune complexes：inhibit ADCC by binding to FcRs on NK cells or macrophages(腫瘤分泌物質把FcRs 佔滿，使其無法與immune complex結合，無法活化ADCC)
19
Q

TNF-α / TNF-β in recombinent cytokine therapy

A
  • TNF-α: 藉由破壞血管內皮(增加內皮細胞的凋亡)來抑制腫瘤的血管新生(angiogenesis)
  • TNF-β :表現出直接的抗腫瘤活性，在保留正常細胞的同時殺死一些腫瘤細胞並降低其他腫瘤細胞的增殖速度

immunology (6 decks)

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