2016 May | Suzanne L. Topalian, Janis M. Taube, Robert A. Anders, and Drew M. Pardoll
The article discusses the development of biomarkers to guide immune checkpoint blockade in cancer therapy, focusing on PD1 and CTLA4 pathways. It highlights the importance of identifying biomarkers that predict therapeutic responses and adverse events, especially with the recent approvals of PD1 and CTLA4 inhibitors. The article explains that the PD1-PDL1 pathway is a dominant immune checkpoint in the tumour microenvironment (TME), and monoclonal antibodies (mAbs) targeting this pathway have shown significant efficacy in melanoma, non-small-cell lung cancer (NSCLC), and renal cell carcinoma (RCC). However, not all cancer types respond to PD1 inhibitors, and biomarkers are needed to guide patient selection and treatment sequencing.
The article discusses the mechanisms of immune checkpoint pathways, including PD1, PDL1, and CTLA4, and their roles in immune suppression. It emphasizes the importance of understanding the biological mechanisms underlying these pathways to develop effective biomarkers. The article also highlights the role of tumour mutational burden and neoantigens in predicting response to immune checkpoint inhibitors. It discusses the challenges in developing reliable biomarkers, including the variability in PDL1 expression and the need for more comprehensive immune profiling of the TME.
The article also explores the role of genetic mutations in cancer and their potential as biomarkers for immune checkpoint inhibitors. It discusses the importance of mutational load in predicting response to PD1 inhibitors and the role of DNA mismatch repair (MMR) defects in increasing tumour mutational burden. The article concludes that while there is growing evidence supporting the use of biomarkers in guiding immune checkpoint therapy, further research is needed to develop more accurate and reliable biomarkers for different cancer types.The article discusses the development of biomarkers to guide immune checkpoint blockade in cancer therapy, focusing on PD1 and CTLA4 pathways. It highlights the importance of identifying biomarkers that predict therapeutic responses and adverse events, especially with the recent approvals of PD1 and CTLA4 inhibitors. The article explains that the PD1-PDL1 pathway is a dominant immune checkpoint in the tumour microenvironment (TME), and monoclonal antibodies (mAbs) targeting this pathway have shown significant efficacy in melanoma, non-small-cell lung cancer (NSCLC), and renal cell carcinoma (RCC). However, not all cancer types respond to PD1 inhibitors, and biomarkers are needed to guide patient selection and treatment sequencing.
The article discusses the mechanisms of immune checkpoint pathways, including PD1, PDL1, and CTLA4, and their roles in immune suppression. It emphasizes the importance of understanding the biological mechanisms underlying these pathways to develop effective biomarkers. The article also highlights the role of tumour mutational burden and neoantigens in predicting response to immune checkpoint inhibitors. It discusses the challenges in developing reliable biomarkers, including the variability in PDL1 expression and the need for more comprehensive immune profiling of the TME.
The article also explores the role of genetic mutations in cancer and their potential as biomarkers for immune checkpoint inhibitors. It discusses the importance of mutational load in predicting response to PD1 inhibitors and the role of DNA mismatch repair (MMR) defects in increasing tumour mutational burden. The article concludes that while there is growing evidence supporting the use of biomarkers in guiding immune checkpoint therapy, further research is needed to develop more accurate and reliable biomarkers for different cancer types.