Low abundant intestinal commensals modulate immune control of chronic myeloid leukemia stem cells
Hinterbrandner, M.; Ronchi, F.; Rubino, V.; Roemmele, M.; Chiorazzo, T.; Mooser, C.; Ganal-Vonarburg, S. C.; McCoy, K. D.; Macpherson, A. J.; Ochsenbein, A. F.; Riether, C.
Show abstract
Leukemia stem cells (LSCs) are resistant to therapy and immune control. The reason for their resistance to elimination by cytotoxic T cells (CTLs) remains unclear. This study shows that specific low abundant Gram-negative intestinal commensals of the genus Sutterella suppress the anti-leukemia immune response in chronic myeloid leukemia (CML). We found that germ-free and specific opportunistic pathogen-free (SOPF) mice are protected from CML development and that colonization of SOPF mice with Sutterella wadsworthensis, but not other related and unrelated bacterial strains, rescues CML development. A higher prevalence of this microbe resulted in Myd88/TRIF-mediated CTL exhaustion in SPF compared to SOPF CML mice as evidenced by higher surface expression of exhaustion markers on CTLs, a reduced capacity to produce interferon-gamma and granzyme B and to kill LSCs in vitro. These findings provide new insights into the immune control of LSCs and identify Sutterella species as regulators of anti-leukemic immunity in CML.
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