Subtype of Gamma Delta T-Cells Benefits TNBC Patients

According to new research published in Science Translational Medicine, a subtype of gamma-delta T-cell has been found in human breast tissue for the first time, and is statistically linked to better survival in a small group of triple-negative breast cancer (TNBC) patients.

These special gamma-delta T-cells with V delta 1 chains were present in greater concentrations in the breasts of women with triple-negative breast cancer who fared better in outcomes of the disease.

“In practical terms, clinical studies have suggested that human breast cancer, including TNBC, can be vulnerable to immune attack, yet the efficacy of immunotherapies in this indication has been relatively poor,” wrote the authors. “We strongly believe that this may be redressed by shifting therapies away from their unique focus on conventional, adaptive T cell responses and by learning from the natural ecology of the local breast T cell compartment.

“In particular, we believe that this may promote the immunogenicity of tumor tissues that drives and sustains patient-beneficial adaptive responses,” they added.

The tissue samples came from females undergoing breast reduction or risk-reducing mastectomy (29 patients), breast tumor resection (90 patients), or patients undergoing TNBC treatment, according to the paper.

Patient lymphocytes were extracted, cultured, sorted, stained, and DNA was extracted and sequenced accordingly. 

These special cells have previously been isolated and identified in the human gut and skin, but this was the first time they have been identified in breast tissue, the authors revealed. 

Outcomes of the 11 patients with TNBC were tracked. These patients were being treated at the Guy’s and St. Thomas’ Hospital Trust. Five who eventually reached remission and lengthy periods of survival also had relatively high numbers of the special cells, according to the authors.

The other six patients died within two years, and only within that group had high numbers of the cells, the results showed.

Additionally, data revealed that an increased number of the special cells correlated with longer progression-free survival (PFS) and overall survival (OS).

The team is helmed by Adrian Hayday, who made his early mark as one of the co-discoverers of gamma delta T cell receptors nearly four decades ago. Hayday is co-founder of Gamma Delta Therapeutics, which has raised more than £100 million in investment since it was started in 2016.

“These cells are an important part of the complex jigsaw in working out the best way to treat cancer," said Hayday, professor of immunobiology at the Francis Crick Institute and also King's College London. “We're really excited about their potential to fight a range of cancers, including melanoma skin cancer, and believe we can now add breast cancer to that list. We hope to see clinical trials starting over the next couple of years, and new scientific findings like this add to our optimism about their potential.”

REFERENCE

Wu Y, Kyle-Cezar F, Woolf R, et al. An innate-like V1+  T cell compartment in the human breast is associated with remission in triple-negative breast cancer. Sci Transl Med. 11, eaax9364 (2019)