Five key factors predict the response of cancer patients to immunotherapy

Immunotherapy has transformed cancer treatment in recent years by enabling the immune system to attack tumour cells. However, only 20-40% of patients respond positively to immunotherapy, and these rates vary across different types of cancer. Predicting which patients will respond to immunotherapy and which will not is currently a highly active area of research. Numerous studies conducted so far have focused on the specific characteristics of tumours, their microenvironment, or the patient's immune system. As a result, which of the proposed biomarkers represent the same underlying factors or how many independent factors influence the effectiveness of this therapy remains unclear.We have identified five key, independent factors that determine patients' response and survival after receiving checkpoint inhibitors (CPIs), a type of immunotherapy widely used in cancer treatment. These findings provide a reference framework for current and future biomarkers of immunotherapy response. We addressed this issue through a comprehensive analysis of genomic, transcriptomic, and clinical data from 479 patients with metastatic tumours, who received CPI treatment. These data are from a public database generated by the Dutch Hartwig Medical Foundation. We used an unbiased approach to analyse thousands of molecular and clinical features and identified five independent factors that influence response to immunotherapy and patient survivalThe five factors identified are: tumour mutational burden (TMB); effective T cell infiltration; the activity of transforming growth factor beta (TGF-β) in the tumour microenvironment; previous treatment received by the patient; and tumour proliferative potential. These factors in different types of cancer are associated with the response to CPIs and have been validated in six independent cohorts, covering a total of 1,491 patients.