Immunotherapy, using the body’s own immune system to target and destroy cancer cells, is one of the most promising frontiers in cancer research, but many patients do not respond to the therapies for reasons not fully understood. Scientists at the Yale Systems Biology Institute have taken a step closer to understanding how the genetic makeup of cancer cells directs the formation of a cancer and influences the tumor micro environment.
Published in Cell Systems, the researchers profiled genes that drive the formation of tumors using genome-scale in vivo CRISPR screens in hosts with different levels of immune response. Led by Sidi Chen; assistant professor of Genetics at Yale School of Medicine; the scientists mapped genes in mice to identify those known to have potential importance to cell aggression or immunity acquisition.
They found a single, lesser known gene “Prkar1a,” that when deleted from cells led to rapid tumor formation, outgrowing every other gene tested. When removed; this gene also changed the tumor environment, increasing inflammation and altering immune responses. Their findings show that tumor-intrinsic mutations in this specific gene drastically alter the genetic program of cancer cells; and remodel the micro environment of tumors.
Different types of cancer
“How cancer cells evade detection by the immune system and which genes activate which pathways to suppress the immune system is relevant for different types of cancer;” said Adan Codina, a graduate student in the Chen lab and first author of the study. Because The relatively unknown gene is expected to provide researchers with a deeper understanding of how different types of immune suppressive cells are “recruited” to a tumor; and how associated changes can help future classifications of patient responses to different types of immunotherapy.
An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells. It detects a wide variety of agents; from viruses to parasitic worms; and needs to distinguish them from the organism’s own healthy cells and tissues in order to function properly. Detection is complicated as pathogens can evolve rapidly; producing adaptations that avoid the immune system and allow the pathogens to successfully infect their hosts.
To survive this challenge, multiple mechanisms evolved that recognize and neutralize pathogens. Even simple unicellular organisms such as bacteria possess enzyme systems that protect against viral infections. Other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants, fish, reptiles, and insects.
These mechanisms include antimicrobial peptides called defensins; phagocytosis, and the complement system. Vertebrates such as humans have even more sophisticated defense mechanisms. Therefore The immune systems of vertebrates consist of many types of proteins, cells, organs, and tissues, which interact in an elaborate and dynamic network.
As part of this more complex immune response; the human immune system adapts over time to recognise specific pathogens more efficiently. Because This adaptation process is referred to as “adaptive immunity” or “acquired immunity” and creates immunological memory. Therefore Immunological memory created from a primary response to a specific pathogen; provides an enhanced response to secondary encounters with that same; specific pathogen. This process of acquired immunity is the basis of vaccination.