Markers may predict patient response to immune therapy of cancer

September 07, 2020

BOSTON - For many individuals with different types of cancer, immune checkpoint inhibitors can effectively boost their immune system to fight their disease, but not all patients benefit from these medications. Now a team led by investigators at Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) has developed an approach to help identify potential clinical markers that may indicate which patients will respond to immune checkpoint inhibitors and which should be treated with other strategies. The findings are published in the Proceedings of the National Academy of Sciences.

For the study, the scientists developed an approach whereby they implanted breast cancer tumors into mice and then treated the animals with immune checkpoint inhibitors. "We first developed a resection and response bilateral tumor model in which we put one breast tumor in each side of the mouse breast. We then remove one tumor to evaluate the tumor microenvironment and we monitor the response of the other, non-resected, tumor to immune checkpoint blockade, identifying the mouse as a responder or a non-responder," explained lead author Ivy X. Chen, PhD, a former postdoctoral fellow at MGH's E.L. Steele Laboratories for Tumor Biology. Using this model system, the researchers found that the responding tumors contained higher numbers of cancer-killing "cytotoxic" T immune cells and fewer numbers of certain immune suppressor cells early after the start of treatment.

Gene expression analyses of the cytotoxic T cells within the tumors revealed distinct gene signatures distinguishing responders from non-responders--specifically, the presence of T cell activation signals in responding tumors and T cell exhaustion signals in non-responding tumors. "Importantly, we found that these gene signatures for responder and non-responder tumors significantly correlated with responder and non-responder gene signatures derived from patients with melanoma who were treated with immune checkpoint inhibitors, as well as with overall survival in a group of patients with breast cancer," said co-senior author Meromit Singer, PhD, an Assistant Professor in the Department of Data Science at the Dana-Farber Cancer Institute and the Department of Immunology at Harvard Medical School.

The impact of this study may go beyond the identification of novel markers to predict patient response to immune checkpoint inhibitors. "Our study highlights the importance of investigating the dynamic immune modulation of the tumor microenvironment to understand the potential benefit of immunotherapy," said co-senior author Rakesh Jain, PhD, director of the Steele Laboratories at MGH and the A.W. Cook Professor of Radiation Oncology at Harvard Medical School. "We hope to extend our approach to study and discover resistance mechanisms and biomarkers of response to immune checkpoint inhibitors in other tumor types."
-end-
Co-senior author Arlene Sharpe, MD, PhD, the George Fabyan Professor of Comparative Pathology at Harvard Medical School, added, "Ultimately, our goal is to utilize this method to develop combination therapies to boost the effectiveness of immune checkpoint inhibitors and to identify new treatments for patients who are unlikely to respond to these agents."

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH Research Institute conducts the largest hospital-based research program in the nation, with an annual research budget of more than $1 billion and comprises more than 8,500 researchers working across more than 30 institutes, centers and departments. In August 2020 the MGH was named #6 in the nation by U.S. News & World Report in its list of "America's Best Hospitals."

Massachusetts General Hospital

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.