Selective Tregs elimination within tumor using CD25 antibody coupled to near-infrared photoimmunotherapy

Regulatory T cells (Tregs) inhibit immune responses. When considering autoimmune diseases or allergies, this function of Tregs has beneficial effect on host. The same function, however, could be "hijacked" by tumors to evade immune destruction. So far, selective depletion of tumor-associated Tregs has not been achieved in clinical settings.

New paper in Science Translational Medicine suggested novel approach to eliminate tumor-associated Tregs: application of anti-CD25 F(ab)2 fragments coupled to photo-active silica-phthalocyanine dye (IR700)  and exposed to near-infrared photo-immunotherapy (NIR-PIT). 

First, in vitro experiments showed that when CD25+ cells are exposed to anti-CD25 F(ab)2-IR700 and subjected to NIR-PIT, they undergo cell death.

Since tumors accumulate high frequency of Tregs, the authors conducted NIR-PIT experiments in vivo. When tumor-challenged mice were exposed to anti-CD25 F(ab)2-IR700 and subjected to NIR-PIT, the authors observed temporal delay in tumor growth and improved survival. 

Of note, tumors located at the distant sites away from direct exposure of NIR-PIT also display growth delay after anti-CD25 F(ab)2-IR700/NIR-PIT application, indicating system-wide after-effect of local elimination of Tregs by NIR-PIT.

Finally, the authors found that anti-tumor effect of anti-CD25 F(ab)2-IR700/NIR-PIT application was mediated by IFN-gamma derived from CD8 T and NK cells.

In summary, the authors claim that this less invasive procedure could selectively eliminate CD25+ Tregs (but not effector T cells) in tumors  and improve survival of tumor-challenged host.

David Usharauli

IL-2 instructs allergen-specific tissue resident memory TH2 cell development

IL-2 is one of the first cytokines [interleukins] discovered and we still have no clear idea of the extent of its involvement and role within immune system. One reason has to do with the fact that IL-2 "in vitro" and IL-2 "in vivo" behave if completely 2 different cytokines.

So, if I see new paper that could tell us more about IL-2, I can't resist reading it. This week journal Immunity has published one such article. There, the authors showed that IL-2 signaling via its high-affinity receptor IL-2α (also known as CD25) directed development of allergen-specific tissue resident memory TH2 cells. I will discuss only those data that are relevant and unequivocal for the story.

For this study, the authors used class II tetramers and i.v. labeling techniques to identify and track house dust mite (HDM) allergen-specific tissue resident T cells. They showed that primary allergen exposure generates lung tissue resident HDM-specific tetramer-positive CD4 T cells.

These lung tissue resident tetramer-positive CD4 T cells expressed IL-13 upon HDM re-challenge (that identified them as TH2 cells).

Next, using parabiont mouse model the authors showed that tetramer-positive CD4 T cells found in allergen challenged lung tissue were bona fide non-circulatory resident-memory TH2 cells.

Finally, using WT:CD25KO mixed bone marrow chimera mice the authors showed that development of lung tissue resident memory TH2 cells required IL-2 signaling via its high-affinity receptor IL-2α.

In summary, this study suggests that IL-2 signaling via its high-affinity receptor IL-2α is mandatory for resident-memory TH2 cell development. This is addition to already known IL-2 roles in Foxp3⁺ Treg and memory CD8 T cell development. From therapeutic point of view, this is one big mess.

David Usharauli