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.