Basic Principles of Immunology and Immunotherapy in Urologic Oncology

Question 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 ___

Answer 1

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.

Question 2

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

Answer 2

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

Question 3

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

Answer 3

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

Question 4

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

Answer 4

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

Question 5

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

Answer 5

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

Question 6

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

Answer 6

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

Question 7

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

Answer 7

true Prostate cancer may also be driven by chronic inflammation.

Question 8

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

Answer 8

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

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 11

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

Answer 11

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

Question 12

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

Answer 12

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.

Question 13

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

Answer 13

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

Question 14

__ effective in second-line kidney cancer

Answer 14

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

Question 15

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

Answer 15

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

Question 16

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

Answer 16

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

Question 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

Answer 17

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

Question 18

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

Answer 18

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

Question 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

Answer 19

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

Question 20

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

Answer 20

IMMUNE EDITING HYPOTHESIS

Question 21

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

Answer 21

Dysfunctional M2 macrophages

Question 22

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

Answer 22

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

Question 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

Answer 23

PD-L1

Question 24

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

Answer 24

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

Question 25

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

Answer 25

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**

Question 26

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

Answer 26

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

Question 27

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

Answer 27

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).**

Question 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.

Answer 28

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

Question 29

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

Answer 29

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

Question 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.

Answer 30

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

Question 31

prostate cancer develops in an environment characterized by chronic inflammation, as well as a nonproductive:\_\_\_\_

Answer 31

**adaptive CD4 and CD8 T cell response**

Question 32

Bacille Calmette-Guérin in Bladder Cancer . Repeated patterns (PAMPs) on the bacterial cell wall stimulate urothelial cells to secrete \_\_, acting through the toll-like receptors __ and \_. ___ of resident macrophages and dendritic cells by BCG components is also likely but has been less well described.

Answer 32

Repeated patterns (PAMPs) on the bacterial cell wall stimulate urothelial cells to secrete cytokines, acting through the toll-like receptors T**LR-2 and TLR-4.** **Direct activation** of resident macrophages and dendritic cells by **BCG components** is also likely but has been less well described.

Question 33

most tumors involve multiple mechanisms to evade immune-mediated destruction, important of these mechanisms involves T-cell expression of one \_\_\_, which binds to its ligand ___ to effectively limit T-cell proliferation and killing capacity

Answer 33

t-cell expression of one PD-1, which binds to its ligand PD-L1 to effectively limit T-cell proliferation and killing capacity

Question 34

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

Answer 34

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.

Question 35

• Anti-PD-1 is **ineffective/effective** in second-line kidney cancer. •

Answer 35

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

Question 36

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

Answer 36

PD-1/P**D-L1 has not shown** robust monotherapy activity in metastatic prostate cancer