Exam 3 - tumor immunology

Question 1

premise behind the concept “a tumor as a wound that does not heal”

Answer 1

wounds/tumors both characterized as…
1. low-level sustained inflam
2. macrophages/monocytes
3. angiogenesis
4. immunosuppressive and fibrogenic cytokines

Question 2

what molecule is the central mediator of that process

Answer 2

vascular endothelium growth factor (VEG-F) - pro-angiogenic

Question 3

______ _______ reflects the origin of cancer at sites of chronic inflammation

Answer 3

lymphoreticular infiltrate

Question 4

what are the 3 classes of stroma cells of the tumor microenvironment

Answer 4

1. cancer-associated fibroblasts (CAFs)
2. endothelial cells & pericytes (angiogenic vascular cells)
3. infiltrating immune cells - macrophages

Question 5

most abdundant, non-malignant cell type in tumor microenvironment

Answer 5

cancer-associated fibroblasts (CAFs)

Question 6

what activates CAFs

Answer 6

growth factors/cytokines
hypoxia, ROS

Question 7

macrophages non-immune mechanisms of tumor growth promotion

Answer 7

angiogenesis
sustain proliferative signaling via mitogenic growth factors
evade growth suppression via enzymatic disruption of cell-cell or cell-ECM interactions

Question 8

function of CCL2

Answer 8

recruit monocytes into tumor bed

Question 9

function of M-CSF

Answer 9

monocyte differentiation into tumor associated macrophages (TAMs)

Question 10

macrophages immune mechanisms of tumor growth promotion

Answer 10

all to escape immune system
1. immune suppressive cytokines
2. immune checkpoint molecule
3. enzymatic depletion of essential nutrients for anti-tumor T cells

Question 11

primary anatomical locations involved in “cancer immunity cycle”

Answer 11

tumor
tumor-draining LN
blood vessels

Question 12

key cellular players involved in “cancer immunity cycle”

Answer 12

tumor cells
APC
T cells

Question 13

Different types of tumor cell death/release of tumor antigens and how this influences the type of immune response generated

Answer 13

tumor-associated antigens (TAA) presented by APC on MHCI to CD8 T cells = adaptive immune response

immunogenic cell death (necrosis)
tolerogenic cell death (apoptosis)

Question 14

immunogenic cell death

Answer 14

necrosis
stimulatory
pro-inflam
good for anti-tumor T cell response

Question 15

tolerogenic cell death

Answer 15

apoptosis
inhibitory
anti-inflam, no T cells
not good for tumors

Question 16

3 signals for T cell priming/activation

Answer 16

1. MHC-peptide-TCR
2. Co-stimulation of CD80/86 (B7) on APC with CD28 on T cell for IL-2 production, T cell survival/proliferation
3. cytokines

Question 17

CTLA4

Answer 17

co-inhibitory immune checkpoint molecule; opposite of CD28
prevents T cell from surviving/proliferating

Question 18

PD-L1

Answer 18

suppresses anti-tumor T cell response
T cell dysfunction
prevents autoimmunity (prevents T cell from attacking tumor cells)

Question 19

cancer patients have high _____ and ______

Answer 19

CDLA-4
PD-1

Question 20

three phases of immunoediting

Answer 20

elimination (NK cells, monocytes, macrophages, neutrophils, DC, CTL)
equilibrium (incompletely eliminated, small population persists)
escape (escape immune system, grow unchecked)

Question 21

three main mechanisms of NK cell-mediated killing of tumor cells

Answer 21

perforin-granzyme
fas-ligand
antibody-dependent cell-mediated cytotoxicity (ADCC)

Question 22

passive mechanisms by which tumor cells escape immune attack

Answer 22

immunoselection
silencing of tumor antigen expression

Question 23

active mechanisms by which tumor cells escape immune attack

Answer 23

direct secretion of suppressive molecules by tumor cells
immune cell inhibitory proteins (PD-L1)
manipulation of immune system