Dynamic Biomarkers of Response to Anti-Immune Checkpoint Inhibitors in Cancer

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Background

Immune response modulation has allowed for breakthrough progress in the treatment of many solid as well as haematological malignancies. To date, immune check-point inhibitors have been approved as first or second line therapy options in a broadening range of metastatic cancer and increasingly explored in the treatment of early stage tumors. The success of checkpoint inhibitors therapies relies on the observation of potentially long lasting responses in a limited subset of patients, ranging from 10% to 40%, depending on the malignancy subtype. However, in the remaining administered patients, these novel treatments provide a more restricted and shorter lasting effect. Efforts have been made to identify predictive factors of response to immune checkpoint inhibitors, with the aim to prescribe them to patients with a high probability of response and avoid to expose non-responder subjects to their potential side effects. Whilst a range of biomarkers have been investigated, their predictive potential remains unsatisfactory and, to date, the only biomarker used in clinical practice is PD-L1, whose expression in tumor tissues is predictive of response to PD-1 immune checkpoint blockade. However, a proportion, albeit small, of patients with absent PD-L1 tumor expression may still respond to PD-1 blockade, making it difficult to restrict prescription of these therapies solely based on this biomarker. Although other biomarkers have been identified, including tumor mutation burden, mismatch repair deficiency status, immune tumor microenvironment, circulating immune cells and host gut microbiota, none of the candidates tested to date has shown sufficient predictive power to enable their application in the clinical practice. Hence, the search for a biomarker of response to checkpoint inhibitors remains an unmet need.

One promising emerging approach is to focus on dynamic biomarkers, which would allow, when tested in the patient early after exposition to the therapeutic agents, to directly observe the presence or absence of an effective response and, more importantly, to identify those patients presenting an immune response failure. Notably, a number of studies have repeatedly shown a strong correlation between the circulating immune cell populations and the tumor immune infiltrate. This has led to the study of dynamic biomarkers in peripheral blood as potential predictors of response to PD-1 immune checkpoint blockade.

In this Research Topic, we would like to discuss the current advances in the study of dynamic biomarkers as predictors of the response to checkpoint inhibitors therapies in cancer.
We welcome the submission of Case Report, Original Research, Methods and Clinical Trials covering, but not limited to the following subtopics:

- Monitoring specific anti-tumor immune responses to tumor associated antigens and/or neoantigens before and during the course of immune checkpoint inhibitors treatment
- Identification of phenotypic markers in immune cells before and during the course of immune checkpoint inhibitors treatment
- Identification of cytokines/chemokines specifically generated before and during the course of immune checkpoint inhibitors treatment
- Biomarkers associated with treatment related toxicity after treatment with immune checkpoint inhibitors

Topic Editor Dr. Merghou is co-founder of and has equity in Imvaq therapeutics. Dr. Merghou reports grants from Bristol-Myers Squibb, Surface Oncology, Kyn Therapeutics, Infinity Pharmaceuticals, Peregrine Pharmeceuticals, Adaptive Biotechnologies, Leap Therapeutics, Aprea.
The other Topic Editors declare no conflict of interest with regard to the Research Topic theme.

Keywords: Immune Checkpoint Inhibitor (ICI), Programmed cell death protein 1 (PD1), Stable disease (SD), Durable Clinical Benefit (DCB), PD-L1, Dynamic biomarkers

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