As science advances, one of the recent trends that continues to pay dividends is immunotherapy to fight cancers. In many cases, the strategy is to mobilize the immune system to attack tumor cells based on cancer-specific antigens expressed either by the tumor itself or within the tumor microenvironment, either by stimulating normal immune cell function to their new tumor target or by removing the suppression of the immune system that is characteristic of many cancers. The trick is to find a way to attack only the tumor and not normal tissues, and certainly not to somehow trigger autoimmunity. 

Remember once upon a time when I said my first actual laboratory research project involved myelin basic protein? Other than knowing that the mother of one of my high school friends had been diagnosed with it, this was the first real exposure I had with multiple sclerosis. I eventually learned more about the immune system and autoimmunity, and the thought of your own body attacking your literal nerve cells was scary and made me feel for the people who have to live with and manage this disease every day. March happens to be Multiple Sclerosis Awareness Month, which as the name suggests works to make sure the public knows about multiple sclerosis, develops empathy and understanding for afflicted individuals, and encourages participation in events and activities to spread awareness. In this blog, let's explore the disease, current treatment strategies and ongoing research, and ways that you can help both in and out of the lab.

My wife and I used to watch House, M.D. starring Hugh Laurie, in which he was a cranky doctor who happened to be a Holmesian genius in diagnosing rare or mysterious diseases. We are fortunate to have doctors who have much better bedside manner, but as an entertainment option, House was a lot of fun. One of the running gags for fans of the show is that the mystery disease of the week is never lupus, except for the one and only time that it was. My fond memories of this show got me to thinking about how difficult it is to diagnose lupus, and about other autoimmune diseases that still remain mysterious and challenging to treat. I decided to find out how modern medicine is approaching this continuing health issue.

Once upon a time when I was a fledgling science nerd in high school, I started learning about the process of apoptosis, which remains to this day the most studied form of cell death in various functions including organismal development and defense against cancer. As an immunologist-in-training, I also learned about the classical complement pathway that the immune system uses to destroy infected cells, and also necrotic cell death or necroptosis (which is full of really gross pictures if you dare to Google it). Of course, I learned about autophagy in graduate school and really appreciate its utility in normal physiology and disease, while very recently I read about ferroptosis as yet another programmed cell death (PCD) pathway. Right around when the Nobel Prize was awarded to recognize the elucidation of PCD, pyroptosis came about as a novel PCD pathway that is continuing to gain steam in its clinical relevance. It seems logical for cells and organisms to have redundant systems in place to clear away damaged and malignant cells before a health crisis can emerge if the cell evades the primary route of apoptosis.

Before my grandmother passed, she had been battling severe dementia for a very long time, which made it difficult in many ways to have conversations with her. It would take several minutes for her to process who I was, and then it would seem like she would remember me and my family, but she would still have to ask for clarification several times even after we had answered her queries. I am grateful that she is in a better place now, but her challenges in the final years of her life deepened my empathy for people who suffer from dementia, and those who take care of them.

With a background in both immunology and cancer biology, I’ve always had a fascination with the interplay between the body’s immune system and any tumors that might pop up. Originally, it made sense that the immune system would actively seek out and destroy cancerous cells, but the emerging consensus is that the interactions between cancers and host immunity is far more complex. In addition to growing new blood vessels and reprogramming metabolic processes, there appears to be some imbalance between avoiding immune cells while also promoting tumor-infiltrating inflammatory cells to promote its growth. ¹ (Figure 1) Trying to dissect this apparent contradictory relationship between tumors and host immunity remains a hot topic.