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Predictive Immune Modeling of Solid Tumors
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Circulating immune cell dynamics as outcome predictors for immunotherapy in non-small cell lung cancer
Alvaro Marcos Rubio1,2,3, Celine Everaert1,2,3, Eufra Van Damme1,2,3
1VIB UGent Center for Medical Biotechnology, Ghent, Belgium.
Abstract:
The use of immune checkpoint inhibitors (ICIs) continues to transform the therapeutic landscape of non-small cell lung cancer (NSCLC), with these drugs now being evaluated at every stage of the disease. In contrast to these advances, little progress has been made with respect to reliable predictive biomarkers that can inform clinicians on therapeutic efficacy. All current biomarkers for outcome prediction, including PD-L1, tumor mutational burden or complex immune gene expression signatures, require access to tumor tissue. Besides the invasive nature of the sampling procedure, other disadvantages of tumor tissue biopsies are the inability to capture the complete spatial heterogeneity of the tumor and the difficulty to perform longitudinal follow-up on treatment. A concept emerges in which systemic immune events developing at a distance from the tumor reflect local response or resistance to immunotherapy. The importance of this cancer 'macroenvironment', which can be deciphered by comprehensive analysis of peripheral blood immune cell subsets, has been demonstrated in several cutting-edge preclinical reports, and is corroborated by intriguing data emerging from ICI-treated patients. In this review, we will provide the biological rationale underlying the potential of blood immune cell-based biomarkers in guiding treatment decision in immunotherapy-eligible NSCLC patients. Finally, we will describe new techniques that will facilitate the discovery of more immune cell subpopulations with potential to become predictive biomarkers, and reflect on ways and the remaining challenges to bring this type of analysis to the routine clinical care in the near future.
Insights
Blood immune cells offer a promising alternative to tissue biopsies for predicting non-small cell lung cancer (NSCLC) treatment response. Analyzing the
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Immune checkpoint inhibitors (ICIs) are revolutionizing non-small cell lung cancer (NSCLC) treatment.
- Current predictive biomarkers (PD-L1, tumor mutational burden) require invasive tumor tissue biopsies, limiting longitudinal assessment and capturing tumor heterogeneity.
- A paradigm shift is emerging, focusing on the systemic immune 'macroenvironment' reflected in peripheral blood.
Purpose of the Study:
- To review the biological rationale for using peripheral blood immune cell subsets as predictive biomarkers for ICI therapy in NSCLC.
- To discuss novel techniques for identifying new blood-based immune cell biomarkers.
- To explore challenges and future directions for implementing blood immune cell analysis in routine clinical care.
Main Methods:
- Review of preclinical and clinical data on blood immune cell subsets in ICI-treated NSCLC patients.
- Discussion of emerging technologies for immune cell analysis.
- Analysis of the concept of the systemic immune macroenvironment.
Main Results:
- Preclinical studies and preliminary clinical data support the potential of blood immune cell subsets to reflect ICI treatment response.
- Peripheral blood analysis offers a less invasive alternative to tumor biopsies for monitoring treatment efficacy.
- New techniques are being developed to discover novel blood-based immune cell biomarkers.
Conclusions:
- Peripheral blood immune cell analysis holds significant promise for guiding ICI treatment decisions in NSCLC.
- Overcoming challenges in biomarker discovery and clinical implementation is crucial for routine use.
- This approach could enhance personalized immunotherapy strategies for NSCLC patients.
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