A recent study looked at how checkpoint inhibitors may impact the success of immunotherapy for cancer treatment.

Immune homeostasis is crucial for human and animal survival. The immune system is equipped with cells and factors that maintain a critical balance of signals that prevent immune dysfunction. Pathways that ensure this balance are immune checkpoints, and these are essential for the self-tolerance that prevents autoimmunity. Immune checkpoint proteins modulate T-cell responses to self-proteins and antigens, including tumor antigens. The proteins are expressed on the surface of cancer and cytotoxic T cells, and cancer cells use these to evade attack by T cells.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. It is due to the growth of neoplastic B cells in the bone marrow, blood, and lymphoid tissues. People with relapsed/refractory high-risk CLL do not respond to conventional treatments. A possible valuable strategy to design T-cell−based treatment involves the receptor tyrosine kinase-like orphan receptor 1 (ROR1). ROR1 mRNA is found to be highly expressed in CLL cells; however, it is not found to be expressed in other bone marrow–derived cells, including blood cells, or normal adult non-hematopoietic cells. Higher expression of ROR1 in CLL cells was correlated with lower CLL survival. Therefore, ROR1 may play a key role in the progression of CLL.

Minimal change disease (MCD) is a kidney disease characterized by pathology in the glomeruli. The disease has its name because changes associated with it can only be seen via electron microscopy. The effects on the glomeruli lead to its increase in permeability and subsequent severe loss of proteins in the urine. Immunological changes in the kidney tissue are thought to promote the development of MCD. Research studies have suggested that abnormalities in Foxp3 T regulatory (Treg) cells, which control immune homeostasis, are involved in MCD pathogenesis.

The influenza A virus (IAV) is the cause of yearly seasonal flu epidemics and is eliminated by CD8+ cytotoxic T cells. Recognition of infected cells is mediated by T cell receptors composed of two (a and b) glycoprotein chains. These receptors bind viral peptides presented by major histocompatibility complex (MHC) class I molecules on infected cells. Cytotoxic T cell receptors that recognize GILGFVFTL (GIL), the immunodominant epitope of IAV, are produced in people who express the MHC class I molecule HLA-A2.

Acute myeloid leukemia (AML) is a cancer originating from cells of the bone marrow and remains difficult to cure due to relapses. There have been significant advances in the development of immunotherapeutic approaches to various types of cancer. Immunotherapy stimulates the patient’s immune system to destroy cancer cells without the harmful adverse effects seen with conventional chemotherapy.

Myalgic encephalomyelitis, also referred to as chronic fatigue syndrome (ME/CFS), is a debilitating condition with unknown etiology that is characterized by excessive and persistent fatigue with physical or mental exertion, often accompanied by flu-like symptoms, and not relieved by rest. Previous clinical studies suggest that infections caused by intracellular pathogens, such as Epstein-Barr virus, may elicit ME/CFS. Therefore, predisposition to the development of ME/CFS may be associated with an impairment of the immune system.

Hepatitis is an inflammation of the liver caused most commonly by hepatitis viruses. Cytotoxic T cells have essential roles in patients with viral hepatitis. Virus-specific cytotoxic T cells can recognize viral antigens of infected liver cells in collaboration with T helper cells. Despite this function in viral hepatitis, the cytotoxic T cell response is nearly undetectable in patients with chronic hepatitis B or C infections.

Cytotoxic T cells are immune cells important in the destruction of pathogen-infected and tumor cells. This function is dependent on specific recognition of the target cell, through the T cell receptor, and the subsequent secretion of specific lysosomes called lytic granules. One cytotoxic T cell can kill multiple target cells during a given immune response. Therefore, the secretion of lytic granules must be well regulated to ensure that the T cells affect the correct targets.

Long-term or permanent remission of tumors after conventional cancer treatments is an ongoing clinical challenge. Therefore, the development of therapies that can kill a single cancer cell would be valuable in addressing this gap in effective cancer therapy. Immunotherapies are promising options that may fill this gap. Cytotoxic T cells are the main players in antitumor immune responses, and dendritic cells are very efficient in presenting tumor antigens to T cells, triggering tumor-specific cytotoxicity.

The respiratory tract is the most common site for infections, and the nasal cavity is one of the first sites of contact for disease-causing organisms. Lymphoid tissues located in the nasal passages are the target tissue in vaccine development strategies. Nasal-associated lymphoid tissues (NALTs) are essential for the induction of cytotoxic T cell immunity against inhaled pathogens. However, the mechanisms of this immune function are not fully understood.