HLA and Cancer Immunotherapy
Continuing Education Credits
This course recaps the fundamentals of human leukocyte antigens (HLA) functions in normal cells and in the context of cancer. Special attention is provided to classical and nonclassical Class-I HLAs (MHC Class I Antigens) in terms of how alterations of expression shape cancer growth, cancer immune escape, and patient overall survival. Strategies of HLA expression patterns to help design molecular interventions from the clinical forefront are also discussed.
Objectives
- Characterize and discuss basic genetic mutation categories as they apply to cancer cells.
- Describe challenges to the basic immune response to cancer, and discuss cellular mutation.
- Describe and discuss HLA in terms of chromosome location, general function, HLA class nomenclature, alleles, and polymorphisms.
- Discuss cytotoxic T lymphocyte cells (CTLs), as well as HLA's relationship to CTL activation.
- Explain how cancer cells alter HLA to escape CTL.
- Discuss different methods of cancer treatment therapy, and explain how HLA shapes CAR-T cancer immunotherapy response.
- Describe how HLA shapes cancer immune checkpoint inhibitor response.
- Explain how EGFR signaling regulates HLA.
- Explain how EGFR signaling regulates HLA.
- Explain how EGFR signaling regulates HLA.
Course Outline
- Cancer Features Overview
- Overview of Cancer Features
- Overview of Cancer Features, continued
- True or False: Cancer cells are characterized by cumulative genetic mutations that enable cells to defy normal cellular regulatory rules.
- True or False: Inherent genetic mutations are the only risks for cancer.
- The worst-case scenario which optimizes the transformation from a normal cell to cancer cells involves:
- A Brief Overview of Immune Response to Cancer
- Immune Response to Cancer
- Immune Response to Cancer, continued
- True or False: Immune cells with cytotoxic T cells and NK cells, in particular, are trained to distinguish "self" cells from "non-self" cells.
- It is a challenging task for cytotoxic T cells to recognize cancer cells because:
- HLA Overview
- HLA Overview
- HLA Overview, continued
- True or False: HLA genes are highly polymorphic, containing different alleles, and the most polymorphic HLA is HLA-B.
- What are alleles?
- HLA is Pivotal for CTL Activation
- HLA is Pivotal for CTL Activation
- True or False: A dendritic cell (abbreviated as DC) is a major antigen presentation cell (APC) that primes for CTL activation by presenting cancer antigenic peptide to a not-yet-activated cytotoxic T cell (CTL).
- CTLs are T lymphocytes that express CD8 on their cell surface. CTL recognizes and kills cancer cells via:
- Cancer Cells Alter HLA to Escape CTL
- Cancer Cells Alter HLA to Escape CTL
- Cancer Cells Alter HLA to Escape CTL, continued
- True or False: LOH refers to one of the two alleles of a gene that has a mutation.
- Which is not one of the ways cancer cells escape immune surveillance?
- HLA Shapes CAR-T Cancer Immunotherapy Response
- Cancer Immunotherapy
- HLA Shapes CAR-T Cancer Immunotherapy Response
- True or False: CAR-T is a cancer immunotherapy that aims to engineer patients’ own T cells to more effectively recognize cancer cells for targeted destruction.
- Regarding CAR-T, the most widely available and studied gene engineered to express on patients' T cells is:
- HLA Shapes Cancer Immune Checkpoint Inhibitor Response
- HLA Shapes Cancer Immune Checkpoint Inhibitor Response
- HLA Shapes Cancer Immune Checkpoint Inhibitor Response, continued
- True or False: Immune checkpoints serve to make sure that the immune system is not overreacting.
- True or False: The 2018 Nobel Prize in Physiology and Medicine was awarded to the two scientists who had made seminal discoveries of how immune checkpoints inhibit T cells.
- EGFR Signaling Negatively Regulates HLA
- Signaling Pathways
- EGFR Signaling Negatively Regulates HLA
- Targeting EGFR Pathway to Harness Cancer
- True or False: EGFR stands for epidermal growth factor receptor, a kinase once activated. It is also an oncogene whose aberrant activation is crucial for Cyclin D1 to initiate cell cycle progression.
- True or False: EGFR pathway-driven Cyclin D1 activities are carried out by a cascade of events participated in by different components along the signaling pathway.
- References
- References
Additional Information
Level of Instruction: Intermediate
Intended Audience: Medical laboratory scientists, medical laboratory technicians, pathology residents, MLS students, and other health care personnel who have an interest in this subject matter.
Author Information: Dr. Nancy Liu-Sullivan served as a Senior Research Scientist with a specialty in cancer genomics and drug discovery prior to joining the biology faculty at the College of Staten Island (CSI), City University of New York (CUNY), teaching Immunology, Radiation Biology, and General Biology, in addition to mentoring students in cancer research.
The author has no
conflict of interest to disclose.
Reviewer Information:
Laurie Bjerklie, MA, MLS(ASCP)CM, is
a Lead Education Developer. She earned a B.S. in Medical Laboratory Science
from the University of North Dakota and an M.A. in Curriculum and Instruction
from Saint Xavier University. She has over 15 years of experience in higher
education and has held program director and faculty positions in both MLT and
MLS programs.
Dr. Julie Ann West is certified by the American Society for Clinical Pathology (ASCP) as a Medical Laboratory Scientist (MLS) and as a Specialist in Microbiology (SM). In addition, Dr. West has earned a PhD in Public Health - Epidemiology Specialization (emphasis on infectious disease) - and is Certified in Public Health (CPH) by the National Board of Public Health Examiners. Dr. West is experienced as a Technical Specialist in Microbiology and Molecular specialties, Safety Officer, Educator, and Lead in the Veterans Administration Healthcare System, and has prior experience as an Administrative Laboratory Director.
Course Description: This course recaps the fundamentals of human leukocyte antigens (HLA) functions in normal cells and in the context of cancer. Special attention is provided to classical and nonclassical Class I HLAs (MHC Class I Antigens) in terms of how alterations of expression shape cancer growth, cancer immune escape, and patient overall survival. Strategies of HLA expression patterns to help design molecular interventions from the clinical forefront are also discussed.