Study of 241 patients links early changes in tumor environment to response to treatment; 59-gene signature offers predictive research tool, not yet intended for clinical use
For the illustrative photo: CC BY 2.0 license; Photo source: NCI website.
From the Haydan editorial team, according to the Technion announcement
Not all patients receiving cancer immunotherapy respond in the same way. Even when two tumors appear similar before treatment, the cellular environment surrounding them may respond differently in the days and weeks following. A study led by Prof. Dvir Aran of the Technion, along with Dr. Zhongyang Lin and colleagues in Germany, examined whether we can learn about the chances of response from this change.
The work, accepted for publication in the journal Cancer Cell, focuses on immune checkpoint inhibitor therapy. These drugs remove the brakes on immune system activity, but their effectiveness varies between patients. The researchers examined the tumor microenvironment: immune cells and other cells found within and around the tumor.
441 samples throughout treatment
The team compiled a single-cell RNA sequencing atlas of 441 samples from 241 patients across 10 types of cancer. Each patient had samples from different times, before and after treatment began. Analysis of the data identified 77 subtypes of immune and supportive cells, which could be grouped into four recurrent states of the tumor environment.
According to the study, approximately 40% of tumors transitioned between states during treatment. Transition to a more inflammatory and active environment, and in particular to an environment rich in B cells, was associated with a better response and prolonged survival. Persistence to, or transition to, a state dominated by myeloid cells was associated with resistance to treatment. These are statistical relationships between samples and patient status, and there is no proof that any such change in itself causes treatment success.
Is it possible to predict the direction of change in advance?
The researchers developed a signature based on the activity of 59 genes in a sample taken before treatment began. The idea is to assess not only the initial state of the tumor, but also its chances of transitioning to a beneficial immune state later on.
In a test on 1,383 initial samples from 19 independent research groups, the signature predicted response and survival and performed similarly to conventional markers, based on different biological information. The researchers are looking to expand the test, but for now it is a research signature: it is not a validated test for selecting treatment for a particular patient and does not replace the assessment of a medical team.
The study suggests monitoring tumor dynamics following treatment and examining in the future whether it can be influenced. Further validation and appropriate clinical studies will be required to determine whether the approach will improve actual treatment decisions.
Questions and Answers
Is it possible today to choose immunotherapy based on the 59 genes?
No. This is a research signature that has not yet been validated as a clinical tool for selecting treatment.
What changed in about 40% of the tumors?
The classification of the immune cell environment changed between the sample taken before treatment and the sample taken after it.
Does switching to B-rich cells guarantee success?
No. The study found an association between the switch and a better response in the groups tested; it does not allow for a guarantee of an outcome for an individual patient.
The scientific article
Source: Announcement from the investigating institution.
