NEW STUDY. Researchers at the University of Gothenburg and Sahlgrenska University Hospital have taken a step towards the goal of individualizing rectal cancer treatment. By analyzing tumor samples, immunologists and surgeons have jointly identified a biomarker that could offer a new way to predict which patients will benefit the most from chemoradiotherapy prior to surgery.
Rectal cancer is one of the more common forms of cancer, and the tumor is located in the lower 15 centimeters of the intestine. Most people need surgery to cure the disease. Surgery is often preceded by treatment with cytostatics and radiotherapy to shrink the tumor and reduce the risk of relapse.
The right dose for the right patient
As pretreatment can have side effects, we try to select those patients who will benefit the most from it. However, the methods that are currently available for selection are blunt. Today, imaging using MR is primarily used to determine who should receive cytostatics or radiotherapy. Trying to improve these selection methods is high on the agenda for researchers in the field worldwide. The aim is to be able to give the right dose to the right patient at the right time.
“The outcome of our collaboration means that we have come a long way toward being able to offer customized treatment for rectal cancer in the future,” says Eva Angenete, Professor of Surgery at the Institute of Clinical Sciences and a surgeon at Sahlgrenska University Hospital. “However, we need to continue working with the marker in order to validate it in a larger population and, we hope, ultimately bring it into clinical use.”
On the computer screens you can see the multi-color microscopy images that Azar colored and which were then used to count several different cell types at the same time.
Tumor samples from 130 patients form the basis of the current study. Six potential biomarkers were then examined. One of these MxA – a footprint of the cytokine type 1 interferon – in combination with counting the number CD8+ T cells has been shown to correlate with which patients that will respond the best to pretreatment. The results have been published in the journal OncoImmunology.
Specific biomarker
The lead author of the article is Azar Rezapour, a doctoral student in Professor Ulf Yrlid’s group at the Institute of Biomedicine. She has carried out much of the laboratory work behind the results and has also contributed to the analyses and writing.
“I am proud that we were able to identify a specific biomarker in the tumor samples”, says Azar. “We have been able to observe that elevated levels of this biomarker correlate with high activity in the patient’s immune cells, which means that they are very likely to respond well to the treatment.”
The collaboration is now continuing to find biomarkers that can also help to identify the patients who will not respond to pre-treatment.
“Our plan is to extend the immunohistological analyses with assessment of RNA expression in the same tissue,” says Ulf Yrlid, Professor of Mucosal Immunology and Microbiology at the University of Gothenburg. “By conducting a multi-analysis, we can find other properties expressed in the tumor tissue. Taken in combination with the biomarker we have now identified, this could be a method for the early identification of patients who will not respond to pretreatment.”
The collaboration is an excellent example of basic science researchers and clinical researchers working together to find answers to clinically relevant problems, known as translational research. This research approach has contributed to the high scores awarded to the University of Gothenburg and Region Västra Götaland in the Swedish Research Council’s evaluations of the national medical training and research system.
Title: A type I interferon footprint in pre-operative biopsies is an independent biomarker that in combination with CD8+ T cell quantification can improve the prediction of response to neoadjuvant treatment of rectal adenocarcinoma; OncoImmunology; https://doi.org/10.1080/2162402X.2023.2209473
BY: ELIN LINDSTRÖM
