Researchers ‘devastated’ after finding manipulated data in study of pediatric brain tumors – Retraction Watch

Robert Wechsler-Reya

An international group of cancer researchers has lost an influential 2020 paper in Nature Neuroscience after finding problems with the data that prompted an institutional investigation.

The article, “Tumor necrosis factor overcomes immune evasion in p53 mutant medulloblastoma,” represented a potentially major advance in the treatment of brain tumors in children, according to Robert Wechsler-Reya, the director of the Tumor Initiation & Maintenance Program at the Sanford Burnham Prebys Medical Discovery Institute. , in La Jolla, California, and the senior author of the paper, which has been cited 17 times, according to Clarivate Analytics’ Web of Science:

The Nature Neuroscience paper was a key piece of work showing that medulloblastoma cells can evade the immune system by shutting down the expression of an important surface molecule called MHC-I, and showing that this evasion can be overcome by treating cells with a cytokine. called tumor necrosis factor (TNF). It had important implications for the immunotherapy of medulloblastoma and other brain tumors and formed the basis for a clinical trial we hoped to launch earlier this year.

Those plans were shelved, the researcher said, after learning of “anomalies” in the data in February:

The machine used to collect much of the key data in the paper, called a flow cytometer, keeps detailed electronic records of how the data was collected, and examination of this data showed that photomultiplier tube (PMT) voltages selectively were modified for some of the samples within certain experiments. (Normally the voltage is kept the same during an experiment so that the samples can be compared). In particular, the voltage appeared to have been manipulated to make it appear that MHC-I expression had increased in response to TNF when it had not. This type of change was found in a large percentage of the data in the paper. (We also examined the author’s data used in other publications and found no evidence of problems in their data used for those articles.) As a result of these findings, we took three key actions:

First, we immediately contacted the Investigative Integrity Officer at Sanford Burnham Prebys to begin the formal review/investigation/investigation of investigative misconduct. This is an extensive and confidential process, which is now being concluded after a full investigation into misconduct. The purpose of this investigation is to determine whether scientific research is intentional, and if so, what sanctions should be imposed on the person concerned. Once completed, the research findings will be shared with ORI, and they will determine whether actions on their part are appropriate.

Second, the planned clinical trial was suspended (before final regulatory approval of the trial and before any patients had been treated) and eventually cancelled.

Finally, given the anomalies in the data, I asked several members of my lab to repeat the large experiments in the paper. This process took several months, and unfortunately my lab members were unable to replicate many of the key findings. Based on these results, we decided that we could no longer support the conclusions of the article and that it would be appropriate to retract it. I contacted the magazine in June, described what had happened and began the process of withdrawal. After they approved the withdrawal in principle, I worked with them to create the appropriate text, and it was published earlier this week.

According to the notice of withdrawal:

The authors withdraw this article due to issues with the integrity of the data presented. In particular, inconsistencies in the flow cytometry data in Fig. 2d, 4b, 5c,d, 5g,h, 6a,b and 7a-d, and extended data. 2b, 3a-i and 6c-j were found, with selected experimental samples collected at different settings from their corresponding controls. Thus, the data in these figures do not reflect the actual fluorescence of the samples in question. Moreover, we have not been able to replicate the main in vivo findings in the article, including those presented in Fig. 7e-h and Extended Data FIG. 8d-k. These concerns undermine our confidence in the investigation, which is why we want to retract the article in its entirety. We deeply regret this incident and apologize to the scientific community.

Wechsler-Reya added that the experience was “devastating”:

As you can imagine, this was a very difficult and daunting process for me and my lab. This was work we were proud of and excited about, and it was devastating to hear that it was based on manipulated data. I’m glad we had the chance to set the record straight, and happy that colleagues in the field have been supportive and understanding. We continue to work on the mechanisms of immune evasion in childhood brain tumors and remain committed to finding more effective treatments for children with these devastating diseases.

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