Urologist Perspective - Fight Cancer With Immunotherapy

January 29, 2018 | Author: Anonymous | Category: Science, Health Science, Immunology
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Cancer Immunotherapy: Fundamental Concepts and Emerging Role Urology Perspective

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Learning Objectives • Review the evidence supporting the immune system’s role in cancer • Review the characteristics of an immune response • Describe mechanisms of immunotherapy

• Discuss treatment considerations of cancer immunotherapy

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Program Agenda

Introduction to the Immune System Immune System’s Role in Cancer Immunotherapy Landscape Clinical Considerations and the State of Immunotherapy

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Everyday Functions of the Immune System • Principal function— prevent/eradicate infections • Continuously surveils for foreign antigens

Courtesy of Science Source Courtesy of Science Source

• Initial defenses are nonspecific, while specialized defenses mount a targeted response Courtesy of Science Source

Abbas AK, Lichtman AH. Basic Immunology. 3rd ed. 2011.

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Immune Response: Key Components • Antigen – Substance that generates an immune response (eg, proteins of pathogens or tumors)

• Antigen presenting cells (APCs) – Identify and uptake foreign antigens – Present them to T cells

• T cells – Recognize and destroy cells containing foreign antigen

• B cells – Produce antibodies specific to foreign antigens

• Antibody – Protein that can identify and neutralize foreign antigens

• Cytokines – Proteins that are naturally secreted by immune system cells Abbas AK, Lichtman AH. Basic Immunology. 3rd ed. 2011.

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Initiation of Immune Response: Key Components Antigen fragments

Antigen

Naive T-cell Antigen receptors

Activated T-cell

Antigen presenting cell (APC)

Antigen recognition

Effector cells: 1. Activate other immune cells 2. Kill “target cells”

Memory cells: 1. Circulate for months  years 2. Ready to rapidly respond to same antigen again

Activated APC

T-cell interaction

Activation

T-cell activation

Replication of antigen-specific T-cells

T-cells become specialized

Lymphoid Organs Adapted from Abbas AK, Lichtman AH.

Peripheral Tissues Abbas AK, Lichtman AH. Basic Immunology. 3rd ed. 2011.

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Program Agenda

Introduction to the Immune System Immune System’s Role in Cancer Immunotherapy Landscape Clinical Considerations and the State of Immunotherapy

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Hallmarks of Cancer Pathogenesis

Avoiding immune destruction

Deregulating cellular energetics

Evading growth suppressors

Activating invasion and metastasis

Hallmarks of Cancer Pathogenesis (2011)1,2

Sustaining proliferative signaling

Enabling replicative immortality

Inducing angiogenesis Resisting cell death

1. Hanahan D, Weinberg RA. Cell. 2011;144:646-674. 2. Hanahan D, Weinberg RA. Cell. 2000;100:57-70.

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Increased Incidence of Cancer in Immunocompromised Individuals • Malignant tumors develop in individuals with compromised immune systems1-3 Tumor/cancer risk in transplant patients compared to general population1-3 Non-melanoma skin cancer 20-fold and beyond

Non-Hodgkin’s lymphoma Kidney cancer

15-fold

Melanoma

8-fold

Hepatobiliary cancer

5-fold

Bladder cancer 3-fold

Testicular cancer Breast cancer

2-fold

Prostate cancer Colon cancer

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5 10 15 Fold-increase in tumor/cancer risk

1. Kasiske BL, Wang C, et al. Am J Transplant. 2004;4(6):905-913. 2. Le Mire L, Wojnarowska F, et al. Br J Dermatol. 2006;154(3):472-477. 3. Abbas AK, Lichtman AH. Basic Immunology. 3rd ed. 2011.

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Immune Cells Within Tumors Predict Overall Survival • T-cell infiltration within tumors predicts overall survival (OS) in multiple cancer types including bladder cancer1-3

0.2

0.4

0.6

0.8

1.0

T cells (CD8) 80 months)

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