Mass cytometry reveals that specific intratumoral CD4+ T cell subsets correlate with patient survival in FL

T cells play a crucial role in how the body fights follicular lymphoma (FL) according to the results of a study led by Mayo Clinic hematologists Zhi Zhang Yang and Stephen Ansell, that was published in Cell Reports.Dr. Yang and his colleagues were interested in understanding why some patients with FL fare better than others with the disease. 

Key findings

• Using mass cytometry, the team identified at least 12 subsets of intratumoral CD4+ T cells, 3 of which were unique to FL biopsies versus control tissues.
• Of these subsets, the frequency of naive T cells correlated with improved patient survival
• Although total PD-1+ T cell numbers were not associated with patient outcome, specific PD-1+T cell subpopulations were associated with poor survival
• Intratumoral T cells lacking CD27 and CD28 co-stimulatory receptor expression were enriched in FL and correlated with inferior patient outcomes
• In vitro models revealed that CD70+ lymphoma cells played an important role in expanding this population. Taken together, the team’s mass cytometry results identified CD4+ memory T cell populations that are poorly functional due to loss of co-stimulatory receptor expression and are associated with inferior survival in FL

Taken together, this study found that patients who had a poor immune response to the disease exhibited a reduction in costimulatory receptors on their T cells. "The presence of costimulatory receptors on the cell surface allows the immune system to better recognize and attack cancer cells," says Dr. Yang. "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 says that, while this research is preclinical and preliminary, it eventually may have clinical implications. "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."

Reference

Yang Z.Z. et al. Mass Cytometry Analysis Reveals that Specific Intratumoral CD4+ T Cell Subsets Correlate with Patient Survival in Follicular Lymphoma. Cell Reports. 2019 Feb 19; 26: 2178–2193; DOI: 10.1016/j.celrep.2019.01.085