Published in Advances in Radiation Oncology: Superhuman Cells are Associated with Improved Response and Outcomes in Lung Cancer Patients

Given varying treatment outcomes in response to therapies, precision medicine enables researchers to identify which patients could benefit most from certain treatments. For patients with unresectable cancers such as locally advanced non-small cell lung cancer (NSCLC), a combination of chemotherapy, radiation, and immune checkpoint inhibitors have been shown to improve survival. Despite this, these therapies can have harmful side effects, especially if the doses are increased for patients who do not show an initial response. Identifying biomarkers that can predict which patients may or may not respond to therapy can help to tailor treatments, prevent unnecessary side effects, and better determine treatment pathways to improve patient outcomes.

Fluorodeoxyglucose-positron emission tomography, or FDG-PET, imaging during chemoradiation treatment for NSCLC has recently been associated with treatment response and patient survival. This type of imaging provides both functional and anatomical information about tumors, giving clinicians a better understanding of tumor size and activity.1 In NSCLC patients undergoing treatment, a significant decrease in FDG-PET uptake values was associated with improved survival after 2 years and, based on these results, FDG-PET is currently being explored as an option to monitor NSCLC patients. However, while useful as a biomarker, FDG-PET is expensive and requires much higher doses of radiation compared to traditional computed tomography (CT).2 Therefore, the identification of other biomarkers that correlate with FDG-PET and NSCLC outcomes is needed, as it could lead to lower costs and safer options for stratifying patients for personalized treatment.

One of the most widely used forms of treatment, chemoradiation, is most effective when patients’ immune cells are active and can mount an anti-tumor response, thus assessing immune cell function prior to treatment could help predict how patients will respond to certain therapies.3 IsoPlexis’ single-cell functional phenotyping has been used in several high-impact studies to identify the “superhero” cells that drive immune response, making immune monitoring a valuable tool for better understanding patient responses and outcomes.

Identifying the Link Between Immune Health and Response

In a study published in Advances in Radiation Oncology, researchers investigated the association of FDG-PET imaging and T cell function in response to chemoradiation in patients with unresectable NSCLC.4 NSCLC patients indicated for chemoradiation, with or without adjuvant durvalumab (an immune checkpoint inhibitor), underwent FDG-PET before, during, and 3 months after chemoradiation.

FDG-PET response was measured after 3 weeks of treatment and used to classify patients as either responders or nonresponders. The researchers also collected blood from a subset of patients before treatment was analyzed to identify the connection between FDG-PET response, therapeutic response, and immune activity. Using IsoPlexis’ single-cell functional proteomics platform, researchers characterized CD8+ T cells by measuring single-cell cytokine secretion. Cells that secrete more than one cytokine are considered polyfunctional and are the key drivers, or “superhero” cells, associated with improved therapeutic response in other malignancies and studies.5,6

When researchers compared the polyfunctionality of CD8+ T cells to FDG-PET response, those who responded to treatment had significantly more polyfunctional cells compared to nonresponders. Furthermore, polyfunctionality was significantly higher in patients who were identified as being disease-free compared to patients who eventually relapsed. This data underscores the importance of functional immune phenotyping as a way to both understand and predict patient response to treatment. As the authors state, “The combination of PET response and peripheral blood biomarkers could be used to guide further clinical trials of treatment intensification by identifying patients at highest risk of treatment failure.”

Using Single-Cell Proteomics to Improve Treatments

The results of the study in Advances in Radiation Oncology emphasize how single-cell functional proteomics can identify and characterize the superhero cells in a population. As drivers of immune response, polyfunctional superhero cells have been shown to be predictive of treatment response across a variety of therapies and cancers. Precision medicine through the characterization of immune cell function at the single-cell level can help clinicians better tailor therapies to patients, resulting in better outcomes and advancements in personalized medicine.

References

  1. Mid-radiotherapy PET/CT for prognostication and detection of early progression in patients with stage III non-small cell lung cancer – ScienceDirect
  2. Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline | Journal of Clinical Oncology (ascopubs.org)
  3. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment – ScienceDirect
  4. Prognostic Value of Early Fluorodeoxyglucose-Positron Emission Tomography Response Imaging and Peripheral Immunologic Biomarkers: Substudy of a Phase II Trial of Risk-Adaptive Chemoradiation for Unresectable Non-Small Cell Lung Cancer (advancesradonc.org)
  5. IsoPlexis’ Single-Cell Proteomics Predict Progression-Free Survival in Melanoma Study | IsoPlexis
  6. Published in JITC – Indications of Immune Health Status: Combination Checkpoint Therapy in Phase II Clinical Trial | IsoPlexis
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