new research in cell report medicine Researchers at the University of Texas MD Anderson Cancer Center have identified key characteristics that may help predict which types of rare cancers are likely to respond to immunotherapy.
In a phase 2 trial of 154 patients with rare cancers led by Aung Naing, MD, professor of cancer therapy, the immunotherapy pembrolizumab had a modest overall response rate of 14.8% and a clinical benefit rate of 26.8%. However, researchers have found that certain other features of the tumor microenvironment may serve as predictive markers of response beyond what can currently be provided by genomic analysis.
This is an important finding because data on rare cancers is difficult to generate. What we have shown in this study is that, beyond traditional responsive genomic markers, several features within the tumor microenvironment may provide new insights into what types of rare cancers respond to immunotherapy. ”
Aung Naing, MD, Professor of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center
Why is this finding important in rare cancers?
Rare cancers, defined as cancers that affect less than 15 cases per 100,000 people annually, collectively account for about one-quarter of cancer deaths in the United States each year. Therefore, treatment of rare cancers is an urgent need, but there are major hurdles.
Despite the challenges of running a rare cancer trial, researchers were able to enroll 154 patients, making it one of the largest immunotherapy studies in the field. A key strength of this trial was that biopsies were collected from the same disease site before and during treatment, allowing researchers to precisely study how tumors and the immune system change in response to treatment.
Several biomarkers are currently being used to determine which rare cancers are likely to respond to immunotherapy, such as microsatellite instability, high mutational burden, or high PD-L1 expression. However, in this trial, a significant number of patients with strong responses did not have tumors with these markers.
This indicates the need to find additional predictive biomarkers. Immunotherapy can improve outcomes for many patients, but identifying patients with rare cancers in particular has been a challenge.
What are the characteristics of the tumor microenvironment and which features have been identified?
Researchers are rapidly learning that the physical characteristics in and around a tumor can be as important as its genomic profile when determining treatment plans. Examples of these include the number of immune cells already present and the density of those cells in a particular area.
By integrating tools that can map and analyze the tumor microenvironment, the research team discovered three new markers to identify rare cancer patients most likely to respond to immunotherapy. These include a pre-existing infiltration of immune cells, particularly CD3 and CD8 T cells, active T cell signaling, and the ability of some tumors with intermediate levels of immune cells to recruit additional immune cells during treatment.
What does this mean for rare cancer patients?
Although this study shows that genomic markers cannot identify all patients who will benefit from immunotherapy, approaches that also leverage analysis of the tumor microenvironment may help physicians improve treatment choices for these patients.
Nain said further research is needed to continue validating these findings, but this study highlights the importance of profiling the tumor microenvironment.
“These types of trials are difficult, but they are also critical to helping us learn more about rare cancers as a population,” said Nine. “While each tumor may be rare, we are increasingly working to understand common characteristics that can inform treatment and help patients receive appropriate treatment more quickly.”
sauce:
University of Texas MD Anderson Cancer Center
Reference magazines:
Nine, A. Others. (2026). Biomarker studies of pembrolizumab in patients with advanced rare cancers. Cell Report Medicine. DOI: 10.1016/j.xcrm.2026.102827. https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00244-2
