class 3

Question 1

Describe the role of myeloid regulatory cells in tumor spreading and metastasis.

Answer 1

Myoid regulatory cells, including macrophages,ritic cells, neutrophils, and myeloid-derived suppressor cells, support tumor growth, spreading, and metastasis by interacting with malignant and immune cells in the tumor microenvironment.

Question 2

What are some factors that modify the tumor microenvironment during tumor progression?

Answer 2

During tumor progression, the tumor microenvironment is modified by a number of growth factors, cytokines, proteases, and other molecules that endorse interaction between malignant and immune cells.

Question 3

How do invasion and metastasis depend on intratumoral vascularization?

Answer 3

Invasion and metastasis depend on intratumoral vascularization, alterations of the basement membrane, and degradation of the extracellular matrix for tumor cell spreading, invasion, and extravasation into the blood and lymphatic vessels.

Question 4

Define pre-metastatic niche and its regulation.

Answer 4

The pre-metastatic niche is the specific microenvironment of an organ or tissue that promotes adhesion and survival of circulating cancerous cells. It is regulated and controlled by bone marrow-derived hematopoietic immune progenitor cells, immature myeloid cells, and certain cytokines, chemokines, and growth factors derived from tumor and immune cells.

Question 5

Do myeloid regulatory cells play a role in the development of pre-metastatic niche?

Answer 5

Yes, myeloid regulatory cells are involved in the regulation and control of the pre-metastatic niche, promoting adhesion and survival of circulating cancerous cells.

Question 6

What is the role of immune cells in tumor progression and metastatic expansion?

Answer 6

Immune cells, including myeloid regulatory cells and lymphoid regulatory cells, mediate the interaction between malignant and immune cells, endorsing tumor progression from initiation through metastatic expansion.

Question 7

Describe the role of myeloid regulatory cells in tumor development and progression.

Answer 7

Myeloid regulatory cells, including myeloid-derived suppressor cells (MDSCs), type 2 or M2 tumor-associated macrophages, regulatory dendritic cells (DCs), type 2 or N2 tumor-associated neutils, and a subset of mast cells, play a key pro-tumorigenic and immunosuppressive role in tumor development and progression.

Question 8

What are the characteristics of myeloid-derived suppressor cells (MDSCs)?

Answer 8

MDSCs represent a heterogenic population of mixed immature bone marrow-derived myeloid cells, including myeloid progenitors and precursors of macrophages, granulocytes, and DCs. They are characterized by a combination of certain phenotypic markers and a strong ability to suppress various T cell functions.

Question 9

How do MDSCs behave in normal conditions versus pathological conditions?

Answer 9

In normal conditions, MDSCs quickly differentiate into mature granulocytes, macrophages, and DCs. In contrast, in pathological conditions such as cancer, infectious diseases, sepsis, trauma, bone marrow transplantation, or some autoimmune disorders, a partial block in the differentiation of immature myeloid cells into mature myeloid cells results in an expansion of this population in different lymphoid and non-lymphoid tissues.

Question 10

Define the association between MDSCs and prognosis in solid tumors.

Answer 10

In solid tumors, infiltration of MDSCs is associated with poor prognosis, and MDSC levels are elevated in the peripheral blood of certain categories of cancer patients. For instance, monocytic MDSCs were enriched in the peripheral blood of melanoma patients compared to healthy donors, and their presence negatively impacted survival and correlated inversely with the presence of functional antigen-specific T cells in patients with advanced melanoma.

Question 11

Describe the potential use of monocytic MDSC frequency as a predictive marker in melanoma patients.

Answer 11

Clinical responders to ipilimumab therapy in melanoma patients showed significantly less monocytic MDSCs compared to non-responders, suggesting that the frequency of monocytic MDSCs may be used as a predictive marker of response, as low frequencies identify patients more likely to benefit from the therapy.

Question 12

Describe the factors associated with expansion of myeloid-derived suppressor cells (MDSCs) in cancer.

Answer 12

Factors associated with MDSC expansion in cancer include tumor-derived secreted factors such as VEGF, S100A8, S100A9, MMP9, and CCL2/MCP-1.

Question 13

How do VEGF, GM-CSF, GCSF, and M-CSF affect myelopoiesis and myeloid cell maturation?

Answer 13

VEGF, GM-CSF, GCSF, and M-CSF up-regulate myelopoiesis and inhibit myeloid cell maturation.

Question 14

What is the impact of late MDSCs on T cell proliferation and antigen-presenting function?

Answer 14

Late MDSCs have increased FKBP51, which reduces suppression of T cell proliferation, and decreased antigen-presenting function.

Question 15

Describe the changes in gene expression related to MDSC immunosuppressive function with tumor growth.

Answer 15

Genes related to MDSC immunosuppressive function, such as S100a8, S100a9, and urokinase (Plau), are increased with tumor growth.

Question 16

Do tumor-derived exosomes have an impact on myeloid cells in the tumor microenvironment and hematopoietic organs?

Answer 16

Yes, tumor-derived exosomes can modulate myeloid cells in the tumor microenvironment and distantly at hematopoietic organs.

Question 17

Describe the major mechanisms suggested for MDSC-mediated suppression of immune cells functioning.

Answer 17

Depletion of amino acids essential for lymphocyte functioning, production of ROS and reactive nitrogen species, interference with lymphocyte trafficking and viability, activation and expansion of regulatory T (Treg) cells, and inhibition of dendritic cell (DC) antigen presentation.

Question 18

Define MDSCs and their role in the tumor microenvironment.

Answer 18

MDSCs are myeloid-derived suppressor cells that can be reprogrammed into regulatory DCs and suppress natural killer (NK) cell cytotoxicity and interferon gamma (IFN-γ) production, aggravating the tumor microenvironment toward malignant development.

Question 19

How do MDSCs induce T cell tolerance and impair T cell activation?

Answer 19

MDSCs induce T cell tolerance via production of free radical peroxynitrite (PNT) and nitration/nitrosylation of TCR and CD8 molecules on the surface of T cells, and impair T cell activation by directly inducing Tregs through the production of IL-10 and TGF-β, or arginase, which is independent of TGF-β.

Question 20

Describe the role of CD11+/Gr-1+ myeloid cells in tumor progression.

Answer 20

These cells are mobilized from the bone marrow by tumor-derived G-CSF and secrete MMP9, S100A8, S100A9, and Bv8 to enhance migration and homing of tumor cells.

Question 21

What is the impact of anti-Bv8 treatment on mice implanted with human tumors?

Answer 21

It results in a reduction of CD11b+ Gr1+ mobilization from the bone marrow, causing a decrease in tumor growth and neoangiogenesis.

Question 22

How do S100A8/A9 heterodimers mediate their effects in the tumor microenvironment?

Answer 22

They block the differentiation of myeloid precursors to differentiated DCs/macrophages through a STAT3-dependent mechanism and chemoattract MDSCs into the tumor through a NF-kB-dependent pathway.

Question 23

Define pre-metastatic niches and their role in tumor progression.

Answer 23

Pre-metastatic niches are supportive microenvironments established in secondary organs by primary neoplastic lesions prior to tumor cell dissemination. They promote tumor cell dissemination through integrin expression and production of various factors in response to tumor/stroma derived factors.

Question 24

Describe the role of hypoxia lysyl oxidase in cancerasis.

Answer 24

Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche, facilitating cancer metastasis.

Question 25

Define myeloid-derived suppressor cells and their impact on the immune system.

Answer 25

Myeloid-derived suppressor cells are regulators of the immune system and are associated with down-regulation of T cell function.

Question 26

How do myeloid progenitor cells in the premetastatic lung promote metastases?

Answer 26

Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition.

Question 27

What is the ‘seed and soil’ hypothesis in the pathogenesis of cancer metastasis?

Answer 27

The ‘seed and soil’ hypothesis revisited explains the pathogenesis of cancer metastasis, emphasizing the interaction between the tumor cells (seed) and the microenvironment (soil) in distant organs.

Question 28

Describe the role of myeloid-derived suppressor cells tumor progression.

Answer 28

Myeloid-derived suppressor cells promote tumor progression by suppressing the immune response and promoting tumor angiogenesis.

Question 29

Define epithelial-mesenchymal transition and its significance in tumor metastasis.

Answer 29

Epithelial-mesenchymal transition is a process where epithelial cells acquire mesenchymal characteristics, facilitating tumor metastasis.

Question 30

How do Gr-1+CD11b+ myeloid cells contribute to tumor promotion in the premetastatic lung?

Answer 30

Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung.

Question 31

What is the significance of immunosuppressive CD14+HLA-DRlow/− monocytes in prostate cancer?

Answer 31

Immunosuppressive CD14+HLA-DRlow/− monocytes play a role in promoting immune suppression in prostate cancer.

Question 32

Describe the induction of myeloid-derived suppressor cells by tumor exosomes.

Answer 32

Tumor exosomes can induce the generation of myeloid-derived suppressor cells, contributing to immune suppression in the tumor microenvironment.