Immune Monitoring Explained

Immune Monitoring and Breakthrough Immunotherapies

More immunotherapies

In Feb 2023, FDA granted the “breakthrough therapy designation” to mRNA-4157/V940, a mRNA cancer vaccine from Moderna, to treat patients with advanced melanoma. This decision was based on their clinical trial results (KEYNOTE-942/mRNA-4157-P201) in which adjuvant treatment using the combo of “mRNA-4157/V940 + KEYTRUDA” reduced the risk of recurrence or death by 44%, compared with using KEYTRUDA alone. This is impressive. And it means that cancer vaccines that people have been talking about for decade is probably not a scientific fiction in the near future.

The core mechanism of cancer vaccine and other immunotherapies is to elicit effective immune responses to tumor-specific antigens (TSA), tumor-associated antigens (TAA), neoantigens, and pathogens. Thus, it is critical to follow and monitor patient’s immune response over the course of a treatment to define the properties of immune system that correspond with successful or unsuccessful therapy. This part of work is done through immune monitoring.

How Immune Monitoring works

The immune monitoring is performed at systemic (peripheral blood) and local (organ/tumor biopsy) levels (see figure below), using a variety of techniques, including immunohistochemistry (IHC), flow cytometry, enzyme-linked immunosorbent assays (ELISA), polymerase chain reaction (PCR), and next-generation sequencing (NGS).

IHC is the most prevalent method to assess immune responses within solid tumors involves enumeration of tumor infiltrating lymphocytes. It allows the visualization of stained immune cells in fixed or live bio-specimens.
Flow cytometry: Cell surface and intracellular markers detected by flow cytometry are regularly used for monitoring the heterogeneity of subsets of cells.
Characterizing immune responses in tumor and blood allows the in-depth profiling of immune cells and a real-time understanding of the dynamic immune system.
Genomic profiling from tumor tissues allows assessing a) immune markers within the tumor microenvironment, b) the influence of genomic mutations on anti-tumor immunity, c) and a predictive variable of response to the therapies.

(The picture is from https://www.frontiersin.org/files/Articles/664244/fimmu-12-664244-HTML-r1/image_m/fimmu-12-664244-g001.jpg)

All these techniques enable researchers and clinicians to evaluate the activation and proliferation of immune cells, the levels of cytokines and chemokines produced by immune cells, and the presence and function of specific immune cell populations (such as T cells, B cells, and natural killer cells). And thus they can determine the efficacy of the treatment.

Recent development in immune monitoring

As immunotherapies have been undergoing feverish development (like the cancer vaccine that we mentioned), many new approaches and techniques have been applied to immune monitoring, especially during clinical trials, to better understand immune response in the tumor microenvironment (TME). Novel frameworks and bioinformatics analysis will allow the integration of extensive data, revealing the power of a much more comprehensive and systemic assessment.

next-generation technologies, such as bulk (RNA and DNA) sequencing, single-cell sequencing,
mass spectrometry with cytometry by time of flight (CyTOF),
“lean and mean” bioinformatics data analysis

(The picture is from https://pubmed.ncbi.nlm.nih.gov/27240055/#&gid=article-figures&pid=figure-1-uid-0)

The significance

Overall, immuno-monitoring is a critical component of immunotherapy, providing valuable insights of the immune response and enabling the development of more effective treatment strategies. Implementing an integrative immuno-monitoring module in research and pharmaceutical development will help guide patient selection, optimize the combination of therapeutic regimens, enhance and predict anti-tumor immunity and clinical responses.

We at Fresh Wind Biotech provide immune-monitoring service, including a full spectrum of bioinformatics data analysis.

We enable clinicians and researchers to process and analyze large and complex data sets generated from these high-throughput platforms, and identify patterns/correlations, and potential biomarkers for immunotherapy. Our bioinformatics analysis can also help in the interpretation and integration of data from multiple sources, enabling more accurate and comprehensive analysis of immune responses.