Hi everyone, I would like to study the effect of tumor-induced exhaustion in NK cell and cytotoxic T cell however any culture protocol of these cell types in vitro so far does not seems to induce a lot of exhaustion markers like TIM-3 and PD-1 in these cell types. Could you suggest me an effective protocol to induce exhaustion in NK cell? Thank you so much!
Dang
Hello Dang,
do you actually find a protocol to induce exhaustion in NK or T cells?
Would be really helpful! Thanks.
Elisabeth
Hi Elizabeth,
Yes, I think repeated stimulations in vitro will likely upregulates genes involved in exhaustion phenotype. Please check this reference below (attached) with signal 1/2 repeated stimulations in T cell induced most the typical markers of exhaustion PD-1, TIM-3 and LAG-3. The protocol was straightforward.
In the case of NK cell, I suppose stimulation with a strong target cell (low ratio) overtime will achieve a similar effect (low antigenic load, prolonged stimulation). Better yet, brief removal of target cells after each stimulation round (either by purification/density centrifugation) can keep the cell mix from overpopulated over time.
Just wondering how successful you are for your T cell exhaustion induction. Can you share any information/experience? Thanks!