Clinical Applications of Immunology ( PART 2)

Tumor antigens recognized by T cells fall into what four categories?

• Mutation (most tumors)

• Tumor-specific Expression (many tumors)- Germ cell lines

• Tissue-specific expression- melanomas prostate (PSA)

• Overexpression (some tumors)- Excessive normal proteins HER2

Overexpression, High or low specificity?

LOW tumor specificity, (some tumors)- Excessive normal proteins HER2

Tissue-specific expression, High or low specificity?

LOW tumor specificity, melanomas prostate (PSA)

Tumor-specific Expression, High or low specificity?

• HIGH tumor specificity, (many tumors)- Germ cell lines

Mutation, High or low specificity?

HIGH tumor specificity, Most tumors

Describe the direct evidence that immunity is important in cancer

• Immune-deficient mice are more susceptible to spontaneous and carcinogen tumors

• Cytokines like Interleukin-2 (IL-2) show anti-tumor activity

• Checkpoint protein inhibition with anti-CTLA-4 antibody is active in melanoma

• Infusion of T cells has anti-tumor efficacy in melanoma

Describe the indirect evidence that immunity is important in cancer

• T cells are actively involved in immune response and surveillance or suppression of tumor cells. EX:

  • In different histologies, usually primary tumors, T cell infiltrate is a positive prognostic factor: In colon cancer immunoscore

  • In melanoma, T cell infiltrate and PD-L1 staining in metastases are important predictive factors with immunotherapy

  • In ovarian cancer, present of T regulatory cells are associated with a poor outcome.

What are the mechanisms of T cell suppression in a tumor microenvironment

• Nutrient deprivation

• Hypoxia

• Metabolic Waste

• Immunosuppressive Factors

Describe immune surveillance and the phases

The immune system can reject cancer via the "Immunoediting" process, which consists of three phases:

• Elimination (surveillance)

• Equilibrium

• Escape

Describe what happens during “elimination” in the Immunoediting process

The Innate and Adaptive immunity destroy the tumor cells before they become clinically apparent

Describe what happens during “equilibrium” in the Immunoediting process

Elimination is not effective, leads to more replication of cancer cells, however the body is able to control it.

Describe what happens during “Escape” in the Immunoediting process

Tumor cell is successfully bypassed the immune system’s recognition, growing unchecked, leads to clinically detectable cancers

Tumor immunity relies on a delicate biological balance between immune ______ and immune ________

• Stimulation

• Inhibition

Describe the Etiology of autoimmune diseases

Genetic Predisposition

• Human leukocyte antigen (HLA) complex

• Family history of autoimmune diseases

Environmental Triggers

• Infections: viral, bacteria, fungal

• Toxins

• Lifestyle

  • Smoking

  • Dietary considerations

Hormonal influences

• Women are more likely to develop autoimmune diseases

  • sex hormones (estrogen)

Describe the pathophysiology of autoimmune diseases

• Breakdown of immune tolerance

• Loss of self-tolerance

• Autoantibody production

• T cell mediated damage

• Immune complex formation

  • Negative/Positive selection (autoantigens to MHC complex)

  • Autoreactive T cells

Describe the clinical presentation of autoimmune diseases

• Fatigue

• Joint pain and swelling

• Skin problems

• Digestive issues

• Systemic symptoms

Describe the treatment principles of autoimmune diseases

• Manage symptoms

• Reduce inflammation (anti-inflammatory meds)

• Suppress the aberrant immune response

• Cure is not typically possible

• Biological therapies:

  • Antibody therapy

  • RNA interference therapy

  • Hematopoietic stem cell transplant therapy

  • Autoantigen based therapies

Define immunotherapy

• Stimulate or boost the immune system

• Provide immune system components

• Targeting and modulating immune responses

Discuss the principles of immunotherapy in the treatment of cancer

• Immune checkpoint inhibitors

• Adoptive cell therapy (CAR T-cell therapy)

• Monoclonal antibodies

• Cancer vaccines

Discuss the principles of immunotherapy in the treatment of Autoimmune diseases

Focus on suppressing the overactive immune tissue response to minimize symptoms and prevent tissue damage

Discuss the principles of immunotherapy in the treatment of Infectious diseases

• Focus on modulating the immune response to pathogens

• Enhance the immune response to help clear the infection or ameliorating immunopathology (damage caused by the immune response itself