A study entitled Precision Immunotherapy was the winner of the Michelson Philanthropies & Science Prize for Immunology. Its author, Aleksandar Obradovic, researcher at Columbia University Irving Medical Center (USA), proposes an individualized approach to identify cell-cell interactions involved in resistance to cancer treatment with immunotherapy.
As Obradovic details in his article, published this week in Science, “in the last decade, cancer treatment has been revolutionized by the emergence of inhibitory immunotherapy, as it activates antitumor immune responses broadly and independently of tumor growth mechanisms. However, many patients do not respond to this therapy and there are no reliable indicators of therapeutic failure.
Developed algorithms help to discern which patients respond or not to cancer immunotherapy
For this reason, it proposes an oncological immunotherapy that is more precise and adapted to each patient. That treatment and single-cell RNA sequencing data would be combined with traditional cancer drugs, using two algorithms developed by his team.
One of them infers protein activity (VIPER) and another predicts drug sensitivity (ARACNe). The goal is to identify groups of cells associated with resistance to treatment in different types of tumors.
“With the vast amount of data missing from single cell RNA sequencing experiments, it is like solving a crossword puzzle”, compares Obradovic, “ARACNe is the dictionary that tells us which letters go with which words, and VIPER is which solves the crossword, finding the correct words even when most of the letters are missing.
The researcher explains to SINC that the algorithms “help to discern the immune characteristics of patients who respond to immunotherapy in two ways: first, the inference of protein activity allows a better resolution of the different cell subtypes present in tumors, as well as the regulation of protein markers of these subtypes.
Next, he points out, “a distinct signature of each cell subtype can be defined and its enrichment verified in large cohorts of patients who responded or not to immunotherapy, determining for each cell type whether it was protective, harmful or neutral. Cell-type informative markers can then be used as novel biomarkers to determine who is most likely to benefit from treatment.”
The specialist points out that “by identifying the regulatory pathways active in cells associated with resistance to immunotherapy, this approach suggests targets to eliminate these cells and, therefore, may lead to the discovery of effective combination therapies in patients who do not respond to immunotherapy. “treatment”.
By identifying the regulatory pathways active in cells associated with resistance to immunotherapy, this approach suggests targets to eliminate them and may lead to the discovery of effective combination therapies.
Aleksandar Obradovic, author of the award-winning essay
To this would be added “the screening of high-performance drugs, which would allow personalizing and quickly prioritizing the optimal combination alternatives for the resistance mechanisms identified in a specific patient”, he emphasizes.
Obradovic says the best hope for the future of his research “is to translate early findings about drug combinations into the design of new clinical trials and patient care,” and he plans to study and integrate the immunological effects of drug combinations into his approach. drugs. .
The benefits of combination therapy
The specialist also points out the benefits of this combined therapy: “A complete understanding of how each treatment option affects tumor cells and the immune cells that surround them can be used to identify resistance markers at an early stage; and thus intervene in these markers with an additional initial therapy, both immunological and targeted”.
Furthermore, “understanding the immune dynamics that come into play with chemotherapy and radiotherapy will also help to determine the timing of drug administration in order to take full advantage of any pro-inflammatory effects,” he concludes.
A. Obradovic. “Precision Immunotherapy”. Science (February 2023).