|Immunotherapy in Neuro-Ophthalmology
|Andrew G. Lee, MD; Praneeth Kambhampati
|(AGL) Chairman, Department of Ophthalmology, The Methodist Hospital, Houston, Texas; Professor of Ophthalmology, Weill Cornell Medicine, New York City, New York; (PK) Class of 2023, Baylor College of Medicine, Houston, Texas
|Immunotherapy; Neuro-Ophthalmology; Cancer; Treatment
|Dr. Lee lectures medical students on immunotherapy in neuro-ophthalmology.
|So today we're going to be talking about immunotherapy. Not the therapy itself, but instead the neuro-ophthalmology of immunotherapy. As you know immunotherapy is very exciting treatment for cancer. The Noble Prize in medicine was awarded for this concept. Under normal conditions as you know, T cells including cytotoxic and T helper cells interact with antigen presenting cells. These antigen presenting cells are in your immune system looking for trouble. [They are] looking for bacteria, looking for foreigners, trying to identify cells that are attacked. When we have an interaction that occurs between the antigen presenting cell and the T cell that is [known as] a MHC complex major histocompatibility complex mediated interaction. It allows the T cell to recognize whether the antigen presenting cell is self or not self. Are you me? Also if that recognition handshake goes well then presenting antigens are not self. There is also MHC 1 versus 2 of course, and that process is really intricately important in general immunity. So whenever we're trying to deal with foreign antigens the T cell is going to ask the antigen presenting cell are you me and if you are me do you have something that's not me. That something that's not me is the antigen. The same process occurs with tumors and that was the innovation of immunotherapy. The T cell is making their contact not with an APC but with a tumor cell. The same process of recognition [occurs] at the MHC. If there's an interaction that says this is the tumor cell the cytotoxic T cell can kill this tumor cell. But the tumor cells are smart and they have developed ways to mask themselves. So normally the interactions that occur again are immunologic are cytotoxic T cell lymphocyte associated receptor and also the programmed cell death receptor. If the tumor can convince the T cell that it's not a tumor it's not foreign, then the T cell won't kill it. That mechanism of evading immune surveillance of cancer is what is allowing this tumor to replicate. However, if we can block that interaction using a PD inhibitor or CTL inhibitor then that is the basis of immunotherapy. By blocking the masquerade of this tumor pretending to be a normal cell we can allow our normal intrinsic adaptive and T cell mediated immunity to kill cancer. That is immunotherapy. You might be saying well that's all well and good Dr. Lee but what does that have to do with ophthalmology. The reason it applies to neuro-ophthalmology is remember that's the same process that's going on over here. So if we block the PD1 or the CTL receptor then we might unleash underlying inflammatory disease. We might unleash cytotoxic T cell and T helper cell interactions with normal healthy cells. The whole purpose of this process is to shield ourselves from auto attack and that self-tolerance requires that recognition site. If we block it then we might get into trouble. Normally Lee's rule of cancer is that if you have cancer and a neuro-ophthalmic problem it's the cancer until proven otherwise. The second most likely thing is a side effect of the treatment of the cancer. Normally because the treatments of cancer are chemotherapies and radiation therapy we only have to think about immunosuppression infections and radiation necrosis. Now that immunotherapy has been added to list we not only have to worry about radiation necrosis, secondary infections, and problems from the treatment like chemotherapy, we have to worry about unleashing inflammatory disease. So, any patient who's got immunotherapy with a blocker at PD1 like Pembrolizumab or at CTL like Emapalumab we have to know that what agent what class of agent is this. We cannot just put there they're on immunotherapy you have to know what class it is. If you have one of these inhibitors on board then we're going to be worried about itis- conjunctivitis uveitis posterior uveitis optic neuritis and endocrine thyroiditis and myasthenia gravis. A whole host of things (have been) will be unleashed by blocking these receptors. So the neuro-op of immunotherapy really boils down to recognizing that autoimmune disease. Both on the afferent side, optic nerve, and on the efferent side, thyroid and myasthenia can occur in patients who are have cancer. So, the new corollary to (rule) Lee's rule of cancer is it could be the cancer, it could be the treatment of the cancer, it can be a side effect of treatment of the cancer, and if it's immunotherapy you should worry about immune disease. This is especially true if it's the checkpoint inhibitor PD1 or CTL.
|Neuro-Ophthalmology Virtual Education Library: Andrew G. Lee Collection: https://novel.utah.edu/Lee/
|North American Neuro-Ophthalmology Society
|Spencer S. Eccles Health Sciences Library, University of Utah, 10 N 1900 E SLC, UT 84112-5890
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