CxImmuno(NoTP)

Immunology and Cancer and Some Concepts on Non-Immunological Host-Response in Cancer

Folder Title: CxImmuno(NoTP) Updated: April 13, 2013 TtlCxImm

Vaccination of Mice with Irradiated Killed Tumor Cells

Figure 15.17 The Biology of Cancer (© Garland Science 2007)

p. 673

Immune Response in Cancer 1. 2. 3. 4. 5. 6. 7.

When it works, what does it “See”? What target or targets does it attack? What “weapons” does it attack with? Why do some tumors regress? Why doesn’t the immune response work better in cancers? Can the immune response in cancer make the pathology worse? How can we make the immune response works better in cancer?

Specific Adaptive Immune Responses: Humoral:AntibodyAntigen (Uses Antibodies to recognize Targets) Cell-Mediated: Helper and Cytotoxic TCells (Uses T-Cell Receptors to Recognize Targets)

Anti-Cancer Effector Mechanisms Humoral: Antibody and complement Lymphokines and other cytokines Cell-Mediated Immunity: Cytotoxic T-Cells Natural Killer Cells (NK Cells) Activated Killer Cells Activated macrophages Lymphokine-activated Lymphocytes Granulocytes Combined Humoral and Cell-mediated: Antibody-dependent Cell-mediated Cytotoxicity

Figure 15.3b The Biology of Cancer (© Garland Science 2007

p. 658)

Figure 15.12d The Biology of Cancer (© Garland Science 2007) p. 666

Potential Tumor Antigen Targets

From Pitot

CxAgsPitot

Login as registered user Ludwig Institute For Cancer Research Academy of Cancer Immunology European Cancer Immunome Program

Please, register before using the database. Registration as a Cancer Immunome Database user is free and open, but necessary for anyone wanting access to the data. If you wish to contribute data to the CID, the username and password that you select guarantee that the information you deposit will be properly attributed, and that you alone (or members of your lab, if the lab is already registered) will have the right to modify it. Please, contact CID manager should you have questions or problems. Have forgotten your password?

http://ludwig-sun5.unil.ch/CancerImmunomeDB/ Cancer Antigen Database: “Immunome” ; Ludwig Institute for Cancer Research

Should the Biology of Cancer course be retained as an undergraduate major course in Biology? This question is set to anonymous. I will not know what choice you selected and this is not graded. Biology of Cancer is not a usual course for a Biology Department. We have had this course going for 35 years. Should we keep it or drop it? (multiple choice)

Responses

Drop it. It belongs in a medical school.

1

1.28%

22

28.21%

55

70.51%

0

0%

78

100%

Keep it, but it needs a lot of improvement to be as valuable as it could be in an undergraduate biology program.

Keep it. It is a valuable option among our undergraduate courses. No opinion on this. Totals 80.00%

0%

70.5%

70.00% 60.00% 50.00%

28,2%

40.00% 28.2%

30.00% 20.00% 10.00%

1.3%

0%

0.00% Drop it. It belongs in a Keep it, but it needs a medical school. lot of improvement to be as valuable as it could be in an undergraduate biology program. Series1

Series2

Keep it. It is a valuable option among our undergraduate courses. Series3

Series4

No opinion on this.

General Concepts on Host-Response in Cancer (Part 1) Does the Host Respond to Prevent Oncogenesis? Does the Host Respond to Limit Neoplastic Growth and Progression? If So, How Does the Host Respond? What Exactly Is the Host Recognizing? • To Prevent Oncogenesis • To Limit Growth and ProgressionGenResp1

General Concepts on Host-Response in Cancer (Part 2) Is the Appearance and Growth of Cancer Related to Weakened Host Response? Genetically Weakened? Environmentally Weakened? Physiologically or Pathologically Weakened? Can Host Response Actually Facilitate Tumor Appearance and Enhance Tumor Growth and Progression? Can the Recognition and Response Mechanisms be Mobilized, Enhanced, and Directed for Cancer Management and Cancer Therapy? Can They Be Used in Cancer Prevention? GenResp2

Cells and Factors in the Natural Immune Response in Cancer Natural Killer (NK) Lymphocytes • Non-B-Cell, Non-T-Cell "Null" Lymphocytes • Activated by Interferon Activated Macrophages • Includes Splenic MPh's, Liver Kupfer Cells, Alveolar (Lung) MPh's, Brain Glial Cells, and others Granulocytes (Polymorphonuclear Leucocytes) • Neutrophils, Eosinophils, Basophils, Tissue Mast Cells Activated Non-Antigen-Specific T-Cells • Lymphokine-activated Killer Cells (LAK) Cytokines • Tumor Necrosis Factor (TNF), Interferons • Interleukins (e.g. IL-2) CxNatImm

Tumor Escape Mechanisms and Immune-mediated Tumor Enhancement 1.

Serum blocking factors

2.

Surface Antigen Shedding

3.

Antigenic Modulation (Internalization of antigens)

4.

Defective complement components

5.

Host genetic limitations

6.

Absence of tumor specific rejection antigenic targets

7.

Localized concentration of effector mechanisms and distant tumor sites and host unresponsiveness.

8.

Immunologically privileged sites.

9.

Immune suppression by viruses, tumor products, illness, or medical intervention (e.g. surgery or radiation)

10. Generation of suppressor cells and suppressor factors 11. Sneaking through by early low levels of tumor targets followed by enhancement or unresponsiveness (tolerance)

Non-Specific Innate Natural Immunity vs Specific Adaptive Immunity in Cancer Innate Natural Immunity Specific Adaptive Immunity No Specific Antigen Recognition Specific Antigen Recognition Not Antibody-dependent Can Involve Antibodies No Antigen-specific T-Cell Receptor Uses T-Cell Receptors Not MHC-Restricted MHC-Restricted (Recognizes Altered-self) No Memory Response Exhibits Immunological Memory No Priming & Second-set Response Enhanced Secondary Responses No Clonal Selection & Expansion Involves Clonal Selection and Expansion of T- and B-Cells Non&Spec

Co-stimulatory and co-receptor molecules in the specific adaptive immune response: Immune escape mechanisms in cancer

MHC Class I Modulation and Escape from T-Cell Lysis

from Kuby, Immunology

MHCEscap

TnBTargets From Pitot

Non-Immunological Host-Responses in Cancer Anti-carcinogenic Effects: Deactivation, Elimination DNA Repair Mechanisms Genetically-directed Apoptosis (May Function in Anti-tumor Immunity Also) Differentiation-inducing Factors Oncolytic Cytokines (May Function in Anti-tumor Immunity Also) Hormonal Responses Anti-Angiogenesis Factors Affecting Tumors Psychological Factors (May Function in Anti-tumor Immunity Also) NonImmRe