Welcome to The Essentials. Before we really get going, we need to lay some groundwork: What is cancer and what exactly is the immune system?
Cancer & The Promise of Immunotherapy
Cancer is (essentially) infinitely complex. This poses SERIOUS problems for traditional cancer therapy. If we are to keep up, we need to shift our mindset.
What Is The Immune System, Really?
Let’s make sure we all understand what the immune system is so we have proper context for the rest of the course.
The Cancer Immunity Cycle
This 7-step cyclical process will provide the framework for the rest of the course. This is not my idea, but it is my graphic!
The innate immune system provides the “first line” of defense against pathogens. Turns out, its pretty good at detecting cancer too.
Cancer Cell-Intrinsic Stress
Cancer cells are like a graduate students: stressed and confused. It’s this intrinsic cell stress that leads to their recognition.
Natural Killer Cell Activation
Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system. They are highly equipped to eliminate stressed cells, like cancer cells.
Innate Phagocytes: Macrophage & Dendritic Cells
Arguably the most important part of the innate immune response is the recruitment and activation of phagocytes, mainly macrophages and dendritic cells.
One of the main goals of the innate immune response is to stimulate the activation of adaptive lymphocytes, T and B cells. Let’s dig in!
Cancer Antigens
First, we need to spend some time discussing what EXACTLY a “Cancer Antigen” is. This lecture will make the T and B cell lessons make way more sense.
Adaptive Lymphocytes: T & B Cells
We have two adaptive cell types, T cells and B cells. These cells are incredibly diverse and their respective receptors enable them to identify a (technically) infinite number of antigens.
T Cell Priming
In order for T cells to do what they do best – kill stuff – they need to be activated by antigen presenting cells like dendritic cells. This is called “T Cell Priming”.
Anti-Cancer T Cell Activity
Now that we have activated CD8+ and CD4+ T cells, what do these things do? How do they actually find and kill cancer cells? Let’s finds out.
B Cell Activation & Differentiation
Unlike T cells, B cells do not induce direct cytotoxicity against their targets. Instead, they differentiate into plasma cells and secrete antibodies.
Antibodies & TIL-Bs
There are three main ways antibodies contribute to the anti-cancer immune response. Also, we need to talk about the newly discovered role of B cells INSIDE the tumor.
Immune Memory
When we get a vaccine, it’s our “immune memory” that keeps us safe for the rest of our lives. Turns out, this memory plays an important role against cancer as well.
Cancer cell metabolism creates extremely harsh conditions within the microenvironment that starves local immune cells of essential nutrients.
“Tumors Are Wounds That Never Heal”
First put forward in the 1980s, the idea that “tumors are like wounds that never heal” perfectly encapsulates several immune evasion mechanisms of solid tumors.
Cancer Cell-Intrinsic Immune Evasion Tactics
As if the last two lessons weren’t enough, the cancer cells themselves can also directly inhibit immune cell activity in three major ways.
Dr. Jeff Martin is a cancer biologist with a PhD in Cancer Genetics and over a decade of experience in immuno-oncology. As the Founder of Oncoleader, Jeff currently advises biotech professionals, providing expert insights on the best ways to navigate the current trends in the immuno-oncology industry.