Therapeutic targets and predictive diagnostics of the immune checkpoint inhibitory therapies

Kocsmár Éva (1), Kocsmár Ildikó (2), Tímár József (1), Lotz Gábor (1)
(1) Semmelweis Egyetem, Patológiai, Igazságügyi és Biztosítási Orvostani Intézet, Budapest
(2) Semmelweis Egyetem, Urológiai Klinika, Budapest

Immune checkpoint inhibitory therapies provide an innovative systemic treatment option alongside chemotherapy and targeted therapies for an increasingly large patient population. These agents are unique in that they restore the anti-tumor defenses of the patient’s own immune system by blocking immune checkpoint molecules that inhibit anti-tumor immunity, such as CTLA4, LAG3, PD-1, PD-L1 proteins. Due to the coordinated operation of immune checkpoints, approaches that simultaneously target multiple immune checkpoints are preferable to over come the evasion of the immune system by tumors and thus represent a promising strategy for immunotherapy of malignant neoplasms. The clinical trials of immuno-oncology drugs has identified a number of factors that may predict treatment success, and their predictive diagnosis is now a routine procedure in pathology and molecular pathology. In the routine diagnostics of PD-L1, it is necessary to use a specific immunohistochemical test dedicated to the particular inhibitor. As the evaluation of these immunohistochemical reactions is very complex and requires a different approach for each tumor type, it is important to be performed in centres by pathologists trained in this field. Cooperation between oncologists and pathologists is also important, as knowledge of the relevant clinical information and treatment plan is essential for the selection and proper evaluation of the appropriate immunohistochemical test.


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