Tumor Immunology Flashcards

1
Q

what role does the immune system play in preventing cancer?

A

catches onto tumor cells that express viral proteins / aberrant self proteins & → eliminates them

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2
Q

what are the categories of tumor cell proteins?

A
  • oncofetal antigens
  • overexpressed normal proteins
  • immunoglobin antigens
  • mutant cellular proteins
  • oncogenic virus proteins
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3
Q

oncofetal antigens

  • are which antigens?
  • are expressed by what tissues?
  • response to tx?
A

AFP, CEA

  • normally ONLY expressed during embryogenesis
  • include
    • carcinoembryonic antigen (CEA): esp elevated in colon cancer
    • alpha-fetoprotein (AFP): esp elevated in liver cancer
  • should decline & stay low if tx is successful
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4
Q

what does it mean if CEA/AFP levels rise after cancer tx?

A

the cancer metastasized, and wasn’t all removed by surgery

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5
Q

which tumor antigens are over-expressed normal proteins?

what tissues are they typically seen in?

A
  • HER-2:
    • breast cancer
    • ovarian cancer
  • CA-125
    • ovarian cancer
    • endometrial / peritoneal inflammation
  • PSA:
    • prostate cancer
    • benign prostatitis
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6
Q

immunoglobin antigens

  • include what antigens?
  • are expressed by what tissues?
A
  • both made during multiple myeloma, which is proliferation of plasma B-cells in the bone → “punch lesions in skeleton”
    • M-protein = MONOCLONAL IG
    • Bence-jones protein = LIGHT CHAINS
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7
Q

what is the most common cause of primary neoplasm in the skeletal system?

A

multiple myeloma

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8
Q

where are bence-jones proteins most likely to be found?

A

= light chains d/t multiple myeloma

in the urine

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9
Q
A

multiple myeloma -“punch lesions” in skeleton

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10
Q
A

multiple myeloma - thick bands = many of one type of Ig being made from proliferating plasma B-cells

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11
Q

mutant cellular gene products

  • includes which antigens?
  • expressed by what mechanisms / tissues?
A

= d/t activation of proto-oncogenes

  • heavy chain locus:
    • in Burkitt’s lymphoma
    • d/t c-myc translocation following an EBV infection
  • mature granulocytes
    • in chronic myelogenous leukemia
    • d/t reciprocal translocation between BCR & ABL
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12
Q

burkitt’s lymphoma

  • mechanism / cause
  • produces what type of tumor antigen?
  • presentation
A
  • antigen type: mutant cellular gene products (activation of proto-oncogenes)
    • EBV infection results in c-myc translocation → heavy chain locus (antigen)
  • presentation - see picture
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13
Q

chronic myelogenous leukemia (CML)

  • mechanism / cause
  • produces what type of tumor antigen?
  • presentation
A
  • antigen type: mutant cellular gene products (proto-oncogene activation)
    • reciprocal translocation of BCR & ABL- genes → mature granulocyte proliferation (antigen)
  • presentation - n/a
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14
Q

what are the presentations of the following oncogenic viral infections?

  • EBV
  • HTLV-1
  • HTVL-2
  • HPV
  • HBV, HCV (hepatitis)
  • HHV-8
A
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15
Q

vaccines are available for which oncogenic viruses?

A
  • HPV - cervical cancer
  • HBV (hepatitis B) - liver cancer
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16
Q

what are the means by which we can detect tumor antigens?

A
  • RAI (radioactive iodine marker):
    • can be used to detect all tumor antigens that shed into the blood/urine:
      • embryonic antigens: CEA, AFP
      • normal antigens that are over expressed: CA-25, PSA
      • myeloma antigens: M-protein, Bence Jones protein

other detection methods:

  • myeloma antigens: with
    • electrophoresis
    • radiography - punch biopsy
  • mutant cellular gene products: with
    • cytogenic analysis - detects translocations
17
Q

what can the “FISH” technique tell us?

A

the # of copies of specific oncogenes

18
Q

outline the immune response to tumors

A
  • involves unique players:
    • macrophages - M1, M2
      • M1 (anti-tumor)
        • = PRO-INFLAMMATORY + ANTI-TUMOROGENIC
          • TNF-a, IL6, 12, 23 → inflammation → cell lysis
      • M2 /TAMs (protumor)
        • ANTI-INFLAMMATORY + PRO-TUMOROGENIC
          • TGF-B, IL-20 → immunosuppressive
          • metalloproteinasesfacilitate tumor cell migration
19
Q

M2 cells

  • are what type of cell?
  • have what role?
  • are produced in what context?
A
  • are specialized macrophages involved in tumor immunity
  • are anti-inflammatory & pro-tumorigenic. produce
    • IL-10, TGF-B
      • immunosuppression
      • fibrosis - encapsulates & protects tumor
      • angiogenesis - vessel growth within tumor
    • metalloproteinases → remodel vasculature to facilitate tumor cell migration
  • are favored in a tumor microenvironment
20
Q

M1 cells

  • are what type of cell?
  • have what role?
  • are produced in what context?
A
  • are specialized macrophage cells involved in tumor immunity
  • are pro-inflammatory & anti-tumorigenic - the “good guys”
    • TNF-a + IL6, 12, 23 → inflammation + cytotoxicity
  • proliferate in response to
    • INF-y
    • LPS
    • TLRs
21
Q

what is the goal of cancer therapy?

A
  • overall: to skew the predominant macrophages from M2 → M1
    • for bladder cancer: instillation of BCG provides TLRs → M1
22
Q

what is the role of NK cells in tumor immunity?

A

= innate immunity

  • NK cells initiate ADCC of tumor cells
    • can detect that have down regulated their MHC-I expression to hide from Tc cells with key receptors:
      • CD16: binds Fc portion of IgG (whose arms are bound to tumor cell antigen)
      • KIR receptors: who CANNOT bind cells with no MHC-I
        • lack of binding sends positive signal of NK cell to → INITIATE ADCC
23
Q

what is the role of B-cells the tumor immunity?

A

= adaptive immunity

produce antibodies (IgG) that participate in ADCC

24
Q

what are the means by which tumors evade our immune system?

A
  • up regulation of PDL-1 expression → Tc inactivation
  • secrete TGF-B & IL-10 → T-cell suppression
  • evasion of T-cells
    • antigen loss variants (tumors that don’t express antigen)
    • Class I MHC down-regulation → evades Tc
    • Lack of B7 → evades Th
  • BCL-2, STAT-3 → prevents apoptosis
25
Q

what is PD-L1?

how does it work?

A
  • a ligand expressed by tumor cells that interact with T-cells that express PD-1 receptor, and → inactivates the Tc
26
Q

what is the role of class I MHC down-regulation immune system evasion by tumor cells?

A
  • helps them escape Tc
  • however, allows them to be seen by NK Cells KIR
27
Q

what tumor cell products can prevent their apoptosis?

A
  • BCL-2
  • STAT-3
28
Q

what are the methods of immunotherapy to treat cancer?

A
  • Mabs - retiuximab, trastuzumab, bevacizumab
  • Checkpoint inhibitors - nivoloumab
  • Adoptive cell transfer
    • CAR-T
    • TILs
    • LAK cells
  • cytokine therapy
29
Q

list the Mabs (monoclonal antibodies) that can be used as cancer immunotherapy?

what type of cancer does each treat?

A
  • rituximab - targets B-cell cancers: targets CD20
  • trastuzumab - targets breast/ovarian cancer → targets HER-2
  • bevacizumab → VEGF (many cancers)
30
Q

what is nivolumab & its role in immunotherapy?

A
  • is an immune checkpoint inhibitor
    • binds & blocks PD-L receptors on activated Tc cells so that they cannot be bound by tumor cells that express PD-L1 → keeps them activated
31
Q

rituximab?

A

tx of cancerous B-cells

targets CD20

32
Q

trastuzumab

A

tx of breast / ovarian cancer

targets HER-2

33
Q

bevacizumab

A

tx of many cancers

targets VEGF

34
Q

list the adoptive cell transfer (ACTs) that can be used as immunotherapy?

what do they all have in common?

A
  • CAR-T
  • TILs
  • LAK cells

all are lymphocytes that are exposed to IL-2 so that they proliferate

35
Q

CART T-cells

  • are engineered how?
  • treat what type of cancer?
A
  • T-cells taken out of individual & genetically engineered to express an surface antigen-receptor with two domains
    • ectodomain: contains surface receptor that binds a specific tumor antigen
    • endodomain: intra-cytoplasm region that conducts signal for Tc cell to be → cytotoxic
  • exposed to IL-2 to → proliferate

good to treat LEUKEMIAS