Anti-IL6 monoclonal antibody, clone 4B6

The tumor microenvironment induces immunosuppression via recruiting and expanding suppressive immune cells such as regulatory T cells (Treg) to promote cancer progression. In this study, we documented that tumor-infiltrating CD73(+) gamma delta Tregs were the predominant Tregs in human breast cancer and exerted more potent immunosuppressive activity than CD4(+) or CD8(+) Tregs. We further demonstrated that cancer-associated fibroblast (CAF)-derived IL6, rather than TGF beta 1, induced CD73(+) gdTreg differentiation from paired normal breast tissues via the IL6/STAT3 pathway to produce more adenosine and become potent immunosuppressive T cells. CD73(+) gamma delta Tregs could in turn promote IL6 secretion by CAFs through adenosine/A2BR/p38MAPK signaling, thereby forming an IL6-adenosine positive feedback loop. CD73(+) gamma delta Treg infiltration also impaired the tumoricidal functions of CD8(+) T cells and significantly correlated with worse prognosis of patients. The data indicate that the IL6-adenosine loop between CD73(+) gamma delta Tregs and CAFs is important to promote immunosuppression and tumor progression in human breast cancer, which may be critical for tumor immunotherapy.

The novel coronavirus, SARS-CoV2, can cause a potentially fatal disease, COVID-19, in humans. Here, we will provide an overview of therapeutic options for COVID-19. Plasma from patients recovered from COVID-19 that contains antibodies against SARS-CoV2 has shown promising results in patients with severe COVID-19. Also, IVIG, combined with moderate-dose of corticosteroids, might improve patient outcomes. Evidence links COVID-19 to variable degrees of inflammation. Studies show that the use of corticosteroids might accelerate recovery from COVID-19. There are, however, no controlled clinical trials that show whether the use of corticosteroids can reduce COVID-19-related death. Also, the pro-inflammatory cytokine IL6 is the best-documented cytokine in COVID-19 correlated with severity, criticality, viral load, and prognosis of patients with COVID-19. Tocilizumab, a monoclonal antibody against IL6, could confer clinical benefit in patients with high IL6 levels. Essential elements that process SARS-CoV2 cell entry and specific characteristics that allow SARS-CoV2 to escape the immune system have the potential as targets for COVID-19 therapy.