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Self-renewal of T-cells and chemoresistance

As you know the fundamental quality of stem cells is self-renewal. Ability to self-renew and differentiate to mature cell types underlies the phenomenon of symmetrical and asymmetrical stem cell division. But not only stem cell can self-renew. It was shown that some subsets of T-lymphocytes (T-cells) can self-renew and divide asymmetrically [1]. But what is biological role of this phenomenon in T-cells? Why do non-stem cells need to self-renew? Can they do it without specific niche? [2]

2 recent studies indicate that self-renewing T-cells form immunological memory in mouse [3] and human [4]. What interests me are the remarkable similarities between self-renewing T-cells and hematopoietic stem cells (HSCs) despite their differing biological functions:

    – Stem-cell like CD8+ memory T-cells express HSC markers: c-Kit+, Rh123-, Sca1+, CD122+;
    – self-renewal could be regulated by pathways in common with those in HSC, such as Wnt;
    – they are quiescent;
    – expressing ABC-superfamily multidrug efflux proteins and chemoresistant.

Why is it significant and what can we learn from this?

    – When you start to search stem-cell-like populations you should apply all of “stemness” markers (surface phenotype, quiescence, metabolic activity, pathways…) and you will find them; It works for many tissues and for cancer(!);
    – Stem-cell-like memory CD8+ T-cells stimulated through Wnt-pathway could be effectively use therapeutically for so-called “adoptive immunotherapy” in cancer and infections;
    – Using Wnt-pathway priming we can theoretically make tumor-specific and antigen-specific T-cell based vaccines. These vaccines could induce long-term T-cell memory and efficiently target intracellular pathogens and cancer;
    – Because adult stem cells, cancer stem cells and self-renewing T-cells share common features (chemoresistance, quiescence…) chasing for efficient killing of the cancer we can also kill memory T-cells and shut down long-lasting immunity after therapy. Bad news.
    – The good news is that stem-cell-like memory T-cells successfully survive anti-cancer chemotherapy and provide immunity against infections after that.

I’d like to finish by quote from the commentary [5]:

However, as the authors themselves state, a more conclusive demonstration of stem cell- like characteristics of this subset (such as serial adoptive transfers) will be required before a clear link to ‘‘memory stem cells’’ can be drawn; this will also require transmission of the findings to suit- able animal models, where more conclu- sive experiments can be performed. Regardless of these limitations, with the currently available data it is tempting to speculate that the CD161hiIL-18Rhi CD8+ memory T cell subset is not only a crucial subset for immune reconstitution during temporary lymphopenia but also a central player in the maintenance of CD8+ T cell memory in healthy individuals.