The measurement of individual biomarkers is generally not considered informative enough. This is because it often fails to adequately capture the intricate interactions within the immune tumour microenvironment (TME). The TME represents a unique aspect of the response to immuno-oncology agents. These interactions are not simple. New checkpoint modulator development, such as PD1/PDL-1 agonists and antagonists, makes this issue particularly apparent. Therefore, multiple potential biomarkers are likely required to gain a better understanding. Relying on one marker does not reflect the sophisticated relationship between the tumour and the innate immune system. Future investigations will likely need to combine several techniques.

Immunotherapy development is an important breakthrough for cancer treatment. Antitumour efficacy has been observed in a wide variety of tumours. To improve the use of immunotherapy, new approaches must be developed. These approaches should help identify which patients are likely to achieve benefit from the treatment. Understanding the ideal choice and sequencing of the numerous available immuno-oncology agents for individual patients is necessary. This understanding helps to minimize therapeutic toxicities. It also helps manage costs. Real-time input from patients and their advocates during biomarker discovery is also required. This is to ensure that the investigations pursued will improve both clinical outcomes and quality of life.

Since multiple biomarkers are likely needed, several candidates are being studied. Current candidates in this area include PD-L1 expression. Another candidate is the presence of CD8+ tumour-infiltrating lymphocytes. Tumour mutation load and the related neoantigen burden are also being examined. Additionally, immune-related gene signatures are under investigation. Multiplex IHC assays represent another category of candidates. These specific assays are used to examine the pharmacodynamic and spatial interactions occurring within the TME. It is thought that the most fruitful investigations will use several of these techniques together. This combination approach helps predict response and interrogate mechanisms of resistance to therapy.

Research into immuno-oncology biomarkers must employ validated assays. This is a requirement for asking focused research questions. These investigations should use clinically annotated tissue collections. Furthermore, biomarker-focused clinical trial designs are needed to investigate specific endpoints. It is suggested that the most effective investigations will likely use several techniques together. This approach can be used to predict patient response and to interrogate mechanisms of resistance. One suggested path forward involves having access to technologies that can recreate the tumour microenvironment in vitro. Merging this capability with the patient’s immune system and multiple endpoint analyses seems to be one way to address the current difficulties in biomarker identification.