Study: Cancer Patients May Need Double Treatment of Immunotherapies

New research from La Jolla Institute for Immunology (LJI) and the University of Liverpool indicates that initiating treatment of patients with cancer with drugs to deplete T follicular regulatory (Tfr) cells may prep the body to respond to subsequent anti-PD-1 therapies and increase overall survival.

Prior research shows that many patients did not respond to anti-PD-1 cancer immunotherapies, or checkpoint inhibitors, and the research team noted that the patients in the current study may have tumors with high numbers of Tfr cells. Anti-PD-1 cancer immunotherapies enhance the body’s cancer-fighting T cells; however, in many patients, suppressive Tfr cells bring that progress to a stop, according to the study authors.

The current study analyzed human tumor samples from 6 cancer types: liver, melanoma, colorectal, non-small lung, head and neck, and breast cancer. The team used single-cell RNA sequencing technology to detect the presence of Tfr cells in these tumors, which showed that tumors resistant to anti-PD-1 therapies also have high numbers of Tfr cells.

“Tfr cells are way more suppressive than normal T regulatory cells, and they stick around longer in tumor tissues,” said first study author and LJI instructor Simon Eschweiler, PhD, in a press release.

Further, Tfr cells are actually activated by anti-PD-1 therapies, which co-senior author and LJI professor Pandurangan Vijayanand, MD, PhD, said can be detrimental when there are a lot of suppressor cells.

“The immune system isn’t getting the boost it is supposed to get from the treatment,” Vijayanand said in the press release. “The brake is on—you aren’t going to go anywhere.”

Selective, sequential immunotherapy treatments may be the best way to help patients with higher numbers of Tfr cells in their tumors, which was discovered while looking specifically at melanoma cases. A retrospective study of 271 patients with melanoma revealed that treating patients with anti-CTLA-4 therapy followed by anti-PD-1 is associated with significantly increased overall survival compared with treating patients with either anti-PD-1 or anti-CTLA-4, or using the 2 treatments at the same time.

The researchers plan to set up a randomized clinical trial with an objective to deplete Tfr cells in cancer patients before giving PD-1 therapy, but the team cautions that depopulating these cells could lead to adverse effects if other types of regulatory T cells are depleted.

“We’re thinking of other ways to deplete this population, outside of anti-CTLA-4 therapies, and we’re collaborating with Cancer Research UK to develop therapeutics that target these cell types,” Vijayanand said in the press release.

REFERENCE

Many cancer patients may need a sequential one-two punch of immunotherapies. La Jolla Institute. Published June 24, 2021. Accessed June 30, 2021. https://www.lji.org/news-events/news/post/many-cancer-patients-may-need-a-sequential-one-two-punch-of-immunotherapies/