Researchers have identified subtypes of T cells occurring within the follicular lymphoma (FL) microenvironment that have differing impacts on patients' chances of survival.
With a median five-year survival of 74% for patients with FL treated with chemoimmunotherapy, this form of treatment has substantially improved outcomes. For a subset of patients who experience early disease progression, however, survival rates remain very low.
Part of the reason for the poor outcome among these patients is an impaired immune response to malignant lymphoma cells. The immune system's T cells are essential to antitumor immunity. Increased overall numbers of T cells within the tumor correlates with a favorable outcome in FL. However, the prognostic significance of intratumoral T cells is far from certain: different subsets of T cells correlate either positively or negatively with patient outcome.
In order to profile T cells within the FL microenvironment, the researchers performed mass cytometry single-cell suspensions from 31 newly diagnosed FL tumors and non-malignant control tissues from healthy individuals. Specimens included three reactive lymph nodes (those fighting off infection), four reactive spleens, and six tonsils. The investigators identified at least 12 subsets of intratumoral CD4+ T cells, three of which occurred uniquely in biopsies of FL tissue and not in healthy tissue samples. The researchers found several interesting results within these subsets.
Higher concentrations of naive T cells, which enable the body to fight off unrecognized infections and diseases, correlated with improved patient survival. In contrast, specific programmed cell death-1 (PD-1)–positive T cell subpopulations were associated with poor survival, even though total numbers of PD-1–positive T cells showed no correlation with patient outcome.
Follicular lymphoma samples had increased quantities of intratumoral T cells that lacked CD27 and CD28 co-stimulatory receptor expression, which correlated with poorer patient outcomes. Cell culture models of FL demonstrated that CD70-positive lymphoma cells played an essential role in increasing the quantities of this subtype of T cells.
"The presence of costimulatory receptors on the cell surface allows the immune system to better recognize and attack cancer cells," explained Zhi-Zhang Yang, MD, a hematologist at Mayo Clinic and lead author of the study, which was published in Cell Reports. "We also found that, among patients with follicular lymphoma, those whose T cells were lacking costimulatory receptors experienced significantly shorter survival than patients whose T cells exhibited costimulatory receptors."
Dr. Yang expressed his hope that these results will one day be of use in clinical settings: "If we can implement a strategy to restore the expression of costimulatory receptors in patients with this subpopulation of T cells, we may be able to develop a new therapy for some patients with follicular lymphoma."
For More Information
Yang Z, Kim HJ, Villasboas JC, et al (2019). Mass cytometry analysis reveals that specific intratumoral CD4+ T cell subsets correlate with patient survival in follicular lymphoma. Cell Rep, 26(8):2178-2193.E3. DOI:10.1016/j.celrep.2019.01.085
Image credit: Alex Ritter, Jennifer Lippincott Schwartz, and Gillian Griffiths, National Institutes of Health