Basic Principles of Immunology and Immunotherapy in Urologic Oncology Flashcards Preview

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Flashcards in Basic Principles of Immunology and Immunotherapy in Urologic Oncology Deck (36)
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1

An immune response begins with an innate response, which is ___ but relatively ___. It then progresses to include the adaptive immune system, which is characterized by both __ and ___

An immune response begins with an innate response, which is rapid but relatively nonspecific. It then progresses to include the adaptive immune system, which is characterized by both specificity and memory.

2

For an antitumor immune response, a Th1 response dominated by (3)  is desired.

2. For an antitumor immune response, a Th1 response dominated by interferon γ, IL-2, and TNF α is desired.

3

CD4+ regulatory T cells (Tregs) __ an adaptive immune response.

CD4+ regulatory T cells (Tregs) inhibit an adaptive immune response.

4

____ explains how early tumors can be recognized and eliminated by the immune system, whereas clinically evident tumors must escape immune recognition to evolve

The immune editing hypothesis explains how early tumors can be recognized and eliminated by the immune system, whereas clinically evident tumors must escape immune recognition to evolve

5

TF/ Prostate cancer may also be driven by chronic inflammation.

Bladder cancer is promoted by ___ initiated by infection or other stimuli

6

In kidney cancer, there is good evidence for an ongoing adaptive, ___ , but paradoxically, an increased __ density is associated with a worse prognosis

In kidney cancer, there is good evidence for an ongoing adaptive, CD8 T-cell–mediated response, but paradoxically, an increased CD8 density is associated with a worse prognosis

7

T/F Prostate cancer may also be driven by chronic inflammation.

true Prostate cancer may also be driven by chronic inflammation.

8

Expression of immune checkpoint molecules on ___ attenuates the adaptive immune response to GU tumors.

Expression of immune checkpoint molecules on tumor-infiltrating lymphocytes (TILs) attenuates the adaptive immune response to GU tumors.

9

BCG therapy for bladder cancer stimulates both the __ and __ and is a prototype for successful cancer immunotherapy.

BCG therapy for bladder cancer stimulates both the innate and adaptive immune systems and is a prototype for successful cancer immunotherapy.

10

Cancer vaccines have been evaluated in both kidney and prostate cancer. A single vaccine ___ is FDA-approved for metastatic prostate cancer

Cancer vaccines have been evaluated in both kidney and prostate cancer. A single vaccine (Sipuleucel-T) is FDA-approved for metastatic prostate cancer

11

Several other vaccine approaches in ___ in kidney and prostate cancer have failed.

Several other vaccine approaches in phase III trials in kidney and prostate cancer have failed.

12

__ interaction is effective in second-line bladder cancer and has activity in first-line patients who are cisplatin-ineligible.

Blocking the PD-1/PD-L1 interaction is effective in second-line bladder cancer and has activity in first-line patients who are cisplatin-ineligible.

13

__ expression may distinguish bladder cancer patients more likely to respond to anti-PD-1/anti-PD-L1 therapy.

PD-L1 expression may distinguish bladder cancer patients more likely to respond to anti-PD-1/anti-PD-L1 therapy.

14

__  effective in second-line kidney cancer

 Anti-PD-1 is effective in second-line kidney cancer

15

Anti-PD-1/PD-L1 has/has not shown robust monotherapy activity in metastatic prostate cancer.

Anti-PD-1/PD-L1 has not shown robust monotherapy activity in metastatic prostate cancer.

16

for innate system: The binding of _ is a fundamental immunologic mechanism though which an organism recognizes “danger.”

The binding of PAMPs to TLRs is a fundamental immunologic mechanism though which an organism recognizes “danger.”

17

___ in the BCG cell wall are canonical PAMPs, which bind to TLR2 on innate immune cells resident in the bladder wall, activating them and initiating a multi-step immune response 

peptidoglycans in the BCG cell wall are canonical PAMPs, which bind to TLR2 on innate immune cells resident in the bladder wall, activating them and initiating a multi-step immune response 

18

For didactic purposes, the immune system is often divided into two subsystems: __ and __

For didactic purposes, the immune system is often divided into two subsystems, the innate and the adaptive

19

sources of bladder inflammation that have been linked to carcinogenesis include chronic urinary tract infections ; chronic indwelling catheters (Groah et al., 2002), and cystitis induced by cyclophosphamide treatment

schistosomiasis hematabium infection, chronic indwelling catheters , and cystitis induced by cyclophosphamide treatment

20

the three phases of tumor/host interactions (elimination, equilibrium, and escape) collectively form the ____ 

IMMUNE EDITING HYPOTHESIS

21

bladder cancer mechanisms similar to those described in other cancers that is, ____ that produce immune suppressive cytokines,

Dysfunctional M2 macrophages

22

__ correlates with outcome in patients with muscle-invasive bladder cancer (Sharma et al., 2007).

 T-cell infiltration correlates with outcome in patients with muscle-invasive bladder cancer

23

 several tissuebased studies showed that the epithelial cells in bladder cancer express the immune checkpoint ligand ___. In one early study,___expression was noted in approximately 15% to 35% of cases, and expression was associated with increased tumor grade 
 

PD-L1

24

PD-L1 was lowly/highly expressed in BGG-induced granulomas in patients progressing on therapy, suggesting a possible ___ mechanism.

Highly expressed, Escape

Mechanistically, these data support a model known as “adaptive immune resistance”  which explains how PD-L1 expression is a critical mechanism by which tumors evade the immune response. In this model, mutations arising as a tumor progresses lead to an adaptive immune response defined by CD8 T cell recognition. These CD8 T cells migrate to the tumor, as a consequence of acquiring effector function secrete the cytokine IFN-γ. IFN-γ is a powerful inducer of PD-L1 expression in tumor cells and myeloid cells and epithelial cells, and it is these induced PD-L1 molecules on tumor cells that interact with PD-1 on the infiltrating CD8 T cells to effectively curtail their antitumor effector function

25

a link between chronic inflammation and kidney cancer is clear/less clear and is suggested with proinflammatory risk factors such as __ or __ (

Unlike bladder and prostate cancer, a link between chronic inflammation and kidney cancer is less clear and is only weakly suggested by the associations of kidney cancer with proinflammatory risk factors such as smoking or obesity

26

In kidney cancer, older and more contemporary data show that an increased ___ is associated with a less favorable outcome.

 

 

In kidney cancer, older and more contemporary data show that an increased CD8 T cell density is associated with a less favorable outcome.

27

In terms of prognosis in kidney ca, one study identified a group of patients with poor outcome with:  

In terms of prognosis in kidney ca, one study identified a group of patients with poor outcome with elevated CD8 T cell infiltration, increased expression of immune checkpoint molecules such as PD-1 and lymphocyte activation gene–3 (LAG-3).

28

RESPONSE TO PROSTATE CANCER
The prostate microenvironment is infiltrated by several types of inflammatory cells, including innate cells such as ___ seven in the absence of symptoms or cancer.

RESPONSE TO PROSTATE CANCER
The prostate microenvironment is infiltrated by several types of inflammatory cells, including innate cells such as macrophages and adaptive cells such as T and B cells even in the absence of symptoms or cancer.

29

chronic inflammation
in the prostate gland is frequently focused in the ___ zone, the region in which more than 90% of tumors arise .

chronic inflammation
in the prostate gland is frequently focused in the peripheral zone, the region in which more than 90% of tumors arise .

30

 prostatic lesion known as __1_, a lesion characterized by flattened, but proliferating, epithelial cells and associated inflammatory cells. Morphologic studies showed that regions of -_1_ are located geographically proximal to high-grade prostatic intraepithelial neoplasia (PIN) lesions ,suggesting a possible causative link between__1__ and the eventual development of cancer.

 prostatic lesion known as prostatic inflammatory atrophy (PIA), a lesion characterized by flattened, but proliferating, epithelial cells and associated inflammatory cells (De Marzo et al., 1999). Morphologic studies showed that regions of PIA are located geographically proximal to high-grade prostatic intraepithelial neoplasia (PIN) lesions (Putzi and De Marzo, 2000), suggesting a possible causative link between PIA and the eventual development of cancer. The adaptive T cell environment of prostate cancer is dominated
by regulatory T cells (Treg), which have been described in the gland itself as well as in neoplastic lesions