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Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
New cytometry tools for immune monitoring during cancer immunotherapy
1Department of Oncology Biomarker Development, Genentech Developmental Sciences, South San Francisco, California, USA.
Insights
Cancer immunotherapy shows promise, but resistance limits effectiveness. Advanced flow cytometry can monitor immune cells in blood to predict treatment outcomes and optimize therapies for better patient benefit.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Cancer immunotherapy (CIT) has advanced significantly, necessitating a deeper understanding of immune system function in health and disease.
- The Human Cell Atlas initiative aims to map all human cells, aiding in the repair of dysfunctional cells.
- Immune checkpoint blockade (ICB) reinvigorates T cells in some cancer patients, but resistance mechanisms limit its universal efficacy.
Purpose of the Study:
- To review advances in understanding how ICB antibodies re-invigorate tumor-specific T cells.
- To highlight recent progress in high-complexity flow cytometry for immune monitoring.
- To emphasize the need for early biomarkers of response and resistance in ICB therapy.
Main Methods:
- Longitudinal analysis of peripheral blood immune cells using flow cytometry as a noninvasive approach.
- Review of high-complexity flow cytometry, including spectral cytometers, for deep immune phenotyping.
- Examination of T cell responses to immune checkpoint blockade.
Main Results:
- ICB antibodies can reinvigorate tumor-specific T cells, leading to durable clinical benefit in a subset of patients.
- Resistance mechanisms to ICB exist, preventing maximal benefit for all treated individuals.
- Advanced flow cytometry enables longitudinal sampling and deep immune phenotyping in clinical settings.
Conclusions:
- Early detection of biomarkers for ICB response and resistance is crucial for patient selection.
- Advanced cytometry platforms and analyses are essential for immune monitoring.
- Optimizing CIT treatments through advanced immune monitoring can maximize clinical benefit for cancer patients.
Abstract:
The success of cancer immunotherapy (CIT) in the past decade has brought renewed excitement and the need to better understand how the human immune system functions during health and disease. Advances in single cell technologies have also inspired the creation of a Human Cell Atlas to identify and describe every cell in the human body with the intention of elucidating how to "fix" the ones that fail normal function. For example, treatment of cancer patients with immune checkpoint blockade (ICB) antibodies can reinvigorate their T cells and produce durable clinical benefit in a subset of patients, but a number of resistance mechanisms exist that prohibit full benefit to all treated patients. Early detection of biomarkers of response and mechanisms of resistance are needed to identify the patients who can benefit most from ICB. A noninvasive approach to predict treatment outcomes early after immunotherapies is a longitudinal analysis of peripheral blood immune cells using flow cytometry. Here we review some of the advances in our understanding of how ICB antibodies can re-invigorate tumor-specific T cells and also highlight the recent advances in high complexity flow cytometry, including spectral cytometers, that allow longitudinal sampling and deep immune phenotyping in clinical settings. We encourage the scientific community to utilize advanced cytometry platforms and analyses for immune monitoring in order to optimize CIT treatments for maximum clinical benefit.

