Immunotherapy's Stroke Risk: What Patients Should Know

Immunotherapy is a treatment for stroke that targets the immune system. Stroke is a cerebrovascular disease with a high mortality rate and can be categorised as either ischemic or hemorrhagic. Immunotherapy works by stimulating the immune system to attack cancer cells, however, this heightened immune response can sometimes become overstimulated or misdirected, causing side effects.

The immune response can impact any tissue or organ, resulting in side effects that range from mild discomfort to severe, potentially life-threatening conditions. These side effects include gastrointestinal issues, flu-like symptoms, respiratory problems, and endocrine disorders.

The side effects of immunotherapy can vary depending on the type of cancer, the immunotherapy treatment plan, the stage of cancer, and the patient's overall health.

Recognising and managing these side effects early on is crucial for maintaining safety and treatment efficacy.

Immunotherapy can cause inflammation and immune dysregulation, which can lead to secondary brain injury

Immunotherapy is a treatment that uses the body's immune system to fight disease. It can be used to treat a variety of conditions, including cancer and stroke. When used to treat stroke, immunotherapy targets the immune cells and inflammatory mediators that are involved in the pathogenesis of secondary injury.

Stroke induces a rapid and large immune response, which can lead to secondary brain injury. This secondary brain injury can be caused by inflammation and immune dysregulation.

Inflammation is a normal part of the body's immune response, but it can sometimes get out of control and cause damage to healthy tissues. In the case of stroke, inflammation can lead to the destruction of the blood-brain barrier, which can then lead to brain edema and other pathological changes.

Immune dysregulation refers to an imbalance in the immune system, which can also lead to secondary brain injury. This can include the activation of the spleen, which can lead to systemic inflammatory responses and immunomodulatory disorders.

The use of immunotherapy to treat stroke is still in the early stages of development, and more research is needed to fully understand its potential benefits and risks. However, initial studies suggest that it may be a promising treatment option for stroke patients.

Immunotherapy can cause systemic inflammation and immunosuppression, increasing the risk of infection

Immunotherapy is a treatment that stimulates the immune system to attack cancer cells. However, this heightened immune response can sometimes become overstimulated or misdirected, causing side effects. These side effects can range from mild discomfort to severe, life-threatening conditions.

When the brain is damaged by a stroke, the immune system becomes hyperactive, leading to a systemic inflammatory response and immunosuppression. This can significantly impact brain damage, recovery, and prognosis. The activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis causes the release of catecholamines, resulting in a surge of stress hormones such as cortisol and adrenaline. This, in turn, leads to immunosuppression, increasing the risk of infection.

The spleen, a crucial organ in the brain-body cross-talk, is affected by the activation of the sympathetic nervous system and the HPA axis, causing splenic contraction and immune dysregulation. This results in a decrease in lymphocytes, which are important for fighting infections. Additionally, the disruption of the blood-brain barrier during a stroke allows the exchange of cytokines and blood cells between the brain and the blood, further propagating the inflammatory response.

The side effects of immunotherapy can vary depending on the type of cancer, the treatment plan, and the overall health of the patient. However, some common side effects related to systemic inflammation and immunosuppression include skin reactions such as rashes and itchiness, gastrointestinal issues like diarrhea, flu-like symptoms, and endocrine disorders. Recognizing and managing these side effects early on is crucial for maintaining the safety and efficacy of immunotherapy treatment.

Immunotherapy can cause activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, leading to splenic contraction and peripheral immune dysregulation

The sympathetic nervous system (SNS) is one of the major neural pathways activated by stress. In situations that are often associated with chronic stress, such as major depressive disorder, the SNS can be continuously activated without the normal counteraction of the parasympathetic nervous system (PNS). As a result, the immune system can be activated with increased levels of pro-inflammatory cytokines. These inflammatory conditions have been repeatedly observed in depression.

The hypothalamic-pituitary-adrenal (HPA) axis and SNS help coordinate proper immune function. After spinal cord injury (SCI), the HPA axis becomes activated and descending input to sympathetic preganglionic neurons (SPNs) is impaired. Lymphoid organs are innervated by SPNs distributed throughout the thoracolumbar spinal cord, so immune suppression after SCI is level-dependent due to activation of the HPA axis and loss of descending input to SPNs.

In the search for the mechanism by which the immune system might contribute to depression, the enhanced activity of indoleamine 2,3-dioxygenase by pro-inflammatory cytokines has been suggested to play an important role. Indoleamine 2,3-dioxygenase is the first enzyme in the kynurenine pathway that converts tryptophan to kynurenine. Elevated activity of this enzyme can cause imbalances in downstream kynurenine metabolites. This imbalance can induce neurotoxic changes in the brain and create a vulnerable glial-neuronal network, which may render the brain susceptible to depression.

Immunotherapy can cause an increase in inflammatory mediators, such as cytokines and chemokines, which can disrupt the blood-brain barrier and cause cerebral edema and neuronal death

Inflammatory mediators are signalling molecules that are released by cells in the immune system. They are involved in the process of inflammation, which is the body's natural response to harmful stimuli, such as damaged cells or foreign pathogens. Inflammatory mediators can be categorised into two groups: pro-inflammatory and anti-inflammatory mediators. Pro-inflammatory mediators, such as cytokines and chemokines, promote inflammation, while anti-inflammatory mediators, such as anti-inflammatory cytokines, help to resolve it.

Cytokines are small proteins that are crucial in cell signalling. They are released by various cells, including immune cells, and act on receptors on target cells to induce a range of responses, such as inflammation. Chemokines are a type of cytokine that have the unique function of acting as chemotactic agents, attracting immune cells to the site of inflammation.

Immunotherapy is a type of cancer treatment that boosts the body's natural defences to fight cancer. It works by activating the immune system to recognise and attack cancer cells. However, immunotherapy can also cause an increase in inflammatory mediators, such as cytokines and chemokines. This increase in inflammatory mediators can have detrimental effects on the brain.

The blood-brain barrier (BBB) is a highly selective semipermeable membrane barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system. It is composed of a layer of endothelial cells that line the capillaries and control the movement of substances between the blood and the brain. The BBB plays a crucial role in maintaining brain homeostasis and protecting the brain from harmful substances.

Inflammatory mediators, such as cytokines and chemokines, can disrupt the BBB by increasing its permeability. This allows immune cells and inflammatory mediators to enter the brain, leading to neuroinflammation. Neuroinflammation is characterised by the activation of glial cells, such as microglia and astrocytes, and the release of pro-inflammatory mediators. This can further increase the permeability of the BBB, creating a positive feedback loop that amplifies the neuroinflammatory response.

Neuroinflammation can have detrimental effects on the brain, including cerebral edema and neuronal death. Cerebral edema refers to the accumulation of excess fluid in the brain, which can increase intracranial pressure and compromise cerebral blood flow, leading to brain damage. Neuronal death, or neurodegeneration, refers to the loss of function and death of neurons, which can have significant impacts on brain function.

Immunotherapy can cause an increase in white blood cell count, which has been associated with worse short-term and long-term functional outcomes in hemorrhagic stroke

The immune system becomes hyperactive when the brain is damaged by a stroke, leading to a systemic inflammatory response and immunomodulatory disorders. This can have a significant impact on brain damage, recovery, and prognosis. The spleen contracts in response to the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, which is thought to be the first link between the central and peripheral immune systems after a stroke. This results in splenic-mediated peripheral immune response, which can lead to systemic inflammatory response syndrome (SIRS).

The systemic inflammatory response contributes to pulmonary infection, kidney infection, and cardiac dysfunction. The release of inflammatory cytokines can also cause dysbiosis and gut inflammation, further increasing the associated cytokines. These circulating pro-inflammatory cytokines can also increase pro-inflammatory T cells, pro-inflammatory macrophages, and classical monocytes, which can access the brain parenchyma through a dysfunctional blood-brain barrier.

In the context of hemorrhagic stroke, studies have shown that an elevated neutrophil-to-lymphocyte ratio (NLR) in peripheral blood is associated with poor functional outcomes. NLR is a surrogate marker of both innate and adaptive immune responses. A recent meta-analysis found that elevated NLR was significantly associated with increased mortality and poor outcomes in acute hemorrhagic stroke. The precise mechanism of splenic contraction in hemorrhagic stroke is not yet known.

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