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Published on: August 15, 2019
Myeloid Cells as Clinical Biomarkers for Immune Checkpoint Blockade
Elisa Peranzoni1, Vincenzo Ingangi2, Elena Masetto2
1Center for Therapeutic Innovation in Oncology, Institut de Recherche International Servier, Suresnes, France.
Abstract:
Immune checkpoint inhibitors are becoming standard treatments in several cancer types, profoundly changing the prognosis of a fraction of patients. Currently, many efforts are being made to predict responders and to understand how to overcome resistance in non-responders. Given the crucial role of myeloid cells as modulators of T effector cell function in tumors, it is essential to understand their impact on the clinical outcome of immune checkpoint blockade and on the mechanisms of immune evasion. In this review we focus on the existing clinical evidence of the relation between the presence of myeloid cell subsets and the response to anti-PD(L)1 and anti-CTLA-4 treatment. We highlight how circulating and tumor-infiltrating myeloid populations can be used as predictive biomarkers for immune checkpoint inhibitors in different human cancers, both at baseline and on treatment. Moreover, we propose to follow the dynamics of myeloid cells during immunotherapy as pharmacodynamic biomarkers. Finally, we provide an overview of the current strategies tested in the clinic that use myeloid cell targeting together with immune checkpoint blockade with the aim of uncovering the most promising approaches for effective combinations.
Insights
Myeloid cells significantly impact cancer patient responses to immune checkpoint inhibitors (ICIs) like anti-PD(L)1 and anti-CTLA-4. Understanding myeloid cell dynamics can improve predicting treatment success and overcoming resistance to ICIs.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet predicting patient response and overcoming resistance remain challenges.
- Myeloid cells critically influence anti-tumor T cell responses and immune evasion within the tumor microenvironment.
- Understanding myeloid cell subsets' role is vital for optimizing ICI efficacy.
Purpose of the Study:
- To review clinical evidence linking myeloid cell subsets to anti-PD(L)1 and anti-CTLA-4 treatment response.
- To explore the utility of myeloid populations as predictive and pharmacodynamic biomarkers in cancer immunotherapy.
- To summarize combination strategies involving myeloid cell targeting and ICIs.
Main Methods:
- Review of existing clinical studies and evidence.
- Analysis of circulating and tumor-infiltrating myeloid cell populations.
- Examination of myeloid cell dynamics during immunotherapy.
Main Results:
- Myeloid cell subsets correlate with patient responses to ICIs across various cancers.
- Circulating and tumor-infiltrating myeloid cells show potential as predictive biomarkers at baseline and during treatment.
- Monitoring myeloid cell dynamics offers insights as pharmacodynamic biomarkers.
Conclusions:
- Myeloid cells are key determinants of ICI efficacy and resistance.
- Targeting myeloid cells in combination with ICIs presents promising therapeutic strategies.
- Further research into myeloid cell-mediated mechanisms can enhance immunotherapy outcomes.
