{"id":407,"date":"2023-09-16T22:09:34","date_gmt":"2023-09-16T21:09:34","guid":{"rendered":"https:\/\/microregistrar.com\/?p=407"},"modified":"2023-09-16T22:09:34","modified_gmt":"2023-09-16T21:09:34","slug":"infection-associated-with-immune-checkpoint-inhibitors","status":"publish","type":"post","link":"https:\/\/microregistrar.com\/?p=407","title":{"rendered":"Infection associated with immune checkpoint inhibitors"},"content":{"rendered":"\n

Immune Checkpoint Inhibitors (ICI) are used to treat malignancy (breast CA, bladder CA, cervical CA, lung CA, colon CA, Hodgkin lymphoma etc). There are three types of ICIs<\/strong><\/p>\n\n\n\n

Type of ICIs<\/strong><\/td>Example<\/strong><\/td><\/tr>
Programmed death 1(PD-1) inhibitors<\/td>Atezolizumab, Avelumab, Durvalumab<\/td><\/tr>
Programmed death 1 ligand (PD-L1) inhibitors<\/td>Nivolumab, Pembrolizumab, Cemiplimab, Dostarlimab<\/td><\/tr>
cytotoxic T lymphocyte-associated antigen 4 (CTLA4) inhibitors<\/td>Ipilimumab, Tremelimumab<\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

How does the ICI work?<\/strong><\/h2>\n\n\n\n

PD-1 and PD-L1 inhibitors<\/strong><\/h4>\n\n\n\n

Activated CD4 and CD8 T-cells express PD-1 on their surface. On coming into contact with the malignant cells, T cells secrete pro-inflammatory cytokines (e.g. IFN\u2010\u03b3). The IFN\u2010\u03b3 upregulate the expression of PD-L1 on tumour cells. PD-1 binds to the PD-L1 to downregulate the T-cell response. This is a natural brake (immune checkpoint) to limit the damage caused by the T cells.<\/p>\n\n\n\n

PD1 and PD-L1 blockers remove this brake and increase the effectiveness of the T cell-mediated damage, leading to better clearance of the malignant cells.<\/p>\n\n\n\n

Unfortunately, as a side effect of this action, the risk of damage to the non-tumour cells is also high. These side effects are called immune-related Adverse Effects<\/strong> (irAE). These irAEs are treated with steroids and infliximab.<\/p>\n\n\n\n

On its own, the ICI usually does not increase the risk of infection significantly. However, the risk of infection increases due to frequent irAEs associated with <\/strong>ICI use. The management of irAEs requires steroids\/infliximab, which causes immunosuppression, increasing the risk of infection.<\/strong>
ICI induced neutropenia has been reported in some patients \u2013 which may increase the risk of infection directly.<\/strong> [Abers, 2020]<\/p>\n\n\n\n

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CTLA4<\/strong> inhibitors<\/strong><\/h4>\n\n\n\n

Another type of checkpoint is CTLA4. When an antigen-presenting cell (APC) presents a foreign antigen (pathogen) to the T cells, it uses two types of signals.
Signal 1 \u2013 MHC on the APC present the foreign antigen to the T-cell receptor.
Signal 2 \u2013 A costimulation process where CD80\/CD86 on the APC interact with the CD28 on the T-cell. This is blocked by CTLA4 (another immune checkpoint). CTLA4 tries to regulate the T cell response to limit the T cell-mediated damage.<\/p>\n\n\n\n

CTLA4 can be blocked by ICIs like Ipilimumab.<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Infections associated with ICIs<\/h2>\n\n\n\n