CAR T-Cell Therapy: A Healthcare Professional's Guide Introduction - The Tumor
Medically reviewed on Oct 22, 2017 by L. Anderson, PharmD.
A Tumor: Defined
When you hear the word tumor, you automatically think of cancer. But what really is a tumor? A tumor, or neoplasm, is a mass of abnormal tissue that arises when cells divided uncontrollably.
However, tumors aren't always a cancer. Tumors can be benign or malignant.
Benign tumors are usually harmless, localized to one area, and are non-cancerous. Benign tumors do not spread but may grow larger, obstructing organs or other structures. Examples of common benign tumors include lipomas, which are composed of fat cells, and angiomas, which consists of small blood vessels.
Malignant tumors (cancer) have the ability to invade surrounding tissues, metastasize (spread throughout the body), and cause significant illness or death.
Malignant Tumor Types
From a histological standpoint, there are over 100 different types of cancer. A cancer is not always a solid tumor mass. Hematologic cancers can form, too, as with leukemia which begins in the blood-forming tissue of the bone marrow. Examples include:
- Sarcomas - arise from bone and soft tissue; examples include osteosarcoma and Kaposi sarcoma.
- Carcinomas - most common form of cancer that arises from epithelial cells; examples include basal cell carcinoma and adenocarcinomas (breast, prostate).
- Lymphomas - begins in lymphocytes (B or T cells); includes non-Hodgkin lymphoma and Hodgkin lymphoma.
- Leukemias - start in the blood-forming tissue of the bone marrow; examples are Acute lymphocytic leukemia (ALL) and Chronic lymphocytic leukemia (CLL).
- Melanomas - originates in melanocyte (pigment) cells leading to skin or eye cancers.
- Myelomas - begin in immune cells called plasma cells that build up in the bone marrow; multiple myeloma results in bone tumors throughout the body.
The Cancer Cell vs. the Normal Cell: What's the Difference?
Cancer cells are less specialized than a normal, healthy cell, and do not have specific biological functions. This allows them to continue dividing and invade surrounding tissues.
Cancer cells can evade apoptosis - the signal that alerts cells to begin programmed cell death and stop dividing.
Cancer cells can take advantage of their microenvironment - for example, they can signal the beginning of angiogenesis when surrounding cells grow blood vessels to help feed the cancer cells.
Cancer cells also can escape or "hide" from the immune system, which normally removes damaged or abnormal cells from the body. In fact, with immunotherapy researchers are now learning how to harness the power of the body's immune system to target and kill cancer cells.
Genetic Drivers of Cancerous Tumor Growth
All cancers have a genetic basis and can occur sporadically or be inherited. The three main cancer-causing genes (oncogenes) that contribute to cancer formation are:
- Proto-Oncogenes: These genes are involved in normal cell differentiation and growth; however, a DNA change can result in these cells growing abnormally and surviving.
- Tumor Suppressor Genes: Normally, these genes also help to control cell growth and division, but mutations can result in cells transforming to malignancies.
- DNA Repair Genes: These genes are responsible for fixing damaged DNA within the cell. However, when these genes are mutated, the cell can develop multiple DNA alterations, giving rise to cancerous cells.
How Do Tumors Escape From the Immune System?
The immune system is simply an amazing part of human biology that has built in mechanisms to clear the body of foreign substances, including cancer cells. However, sometimes things go awry. Common mechanisms that tumors might activate to escape from immune cell clearance include:
- Loss or a change in antigens on the tumor. Tumors can lose the major histocompatibility complex (MHC), a group of genes that normally tell the intracellular machinery to transfer tumor antigens to the surface for T-cell recognition.
- Tumors may be able to create a protective environment altering cytokines (e.g., interferon, interleukin, and growth factors) that block tumor antigen recognition by the T-cell.
- Tumors can increase the expression of PD-1 and PD-L1 immune checkpoint molecules that deplete the cancer-clearing T-cell activity.
Boosting the Immune System With Immunotherapy
Promising immunotherapy drug treatments are now approved, under FDA review, or being developed to augment the immune system and fight off these cancerous tumors. Cancer immunotherapy treatments include:
Finished: CAR T-Cell Therapy: A Healthcare Professional's Guide: Introduction - The Tumor
Connolly JL, Schnitt SJ, Wang HH, et al. Tumor Structure and Tumor Stroma Generation. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Accessed October 22, 2017 from https://www.ncbi.nlm.nih.gov/books/NBK13447/
What is Cancer? National Cancer Institute (NIH). Accessed October 22, 2017 at https://www.cancer.gov/about-cancer/understanding/what-is-cancer
Mandal A. Cancer Pathophysiology. News Medical. Accessed October 22, 2017 at http://www.news-medical.net/health/Cancer-Pathophysiology.aspx
Kakarla S, Gottschalk S. CAR T Cells for Solid Tumors: Armed and Ready to Go? Cancer J. 2014; 20:151-55. AccessedOctober 22, 2017 at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050065/
Targeted Cancer Therapies. National Cancer Institute (NIH). Accessed October 22, 2017 at https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet
Shoushtari A, Snyder Charen A, Postow A, et al. Up to Date: Principles of Cancer Immunotherapy. Accessed October 22, 2017 at https://www.uptodate.com/contents/principles-of-cancer-immunotherapy
CAR T-Cell Therapy: Engineering Patients' Immune Cells to Treat Their Cancers. National Cancer Institute (NIH). Accessed October 22, 2017 at https://www.cancer.gov/about-cancer/treatment/research/car-t-cells
Chimeric Antigen Receptor (CAR) T-Cell Therapy. The Leukemia & Lymphoma Society (LLS). Accessed October 22, 2017 at https://www.lls.org/treatment/types-of-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy
The Genetics of Cancer. National Cancer Institute (NIH). April 2015. Accessed October 22, 2017 at https://www.cancer.gov/about-cancer/causes-prevention/genetics