Systemic bacillus Calmette-Guérin (BCG) activates natural suppressor cells.

Abstract

Addition of normal C57BL/6 mouse bone marrow cells to an in vitro culture of normal C57BL/6 spleen cells and allogeneic P815-Y tumor cells inhibited the development of cell-mediated immunity. Bacillus Calmette-Guérin (BCG) enhanced the suppressive activity of these bone marrow cells as early as 2 days after its intravenous administration to donor mice and elicited similar activity in the spleen by 7 days. Concomitant with the appearance of suppressor cells in the spleen there was a decrease in bone cell number and an increase in spleen cell number. While normal spleen cells failed to inhibit immunization, spleen cells from thymectomized, irradiated, bone marrow-reconstituted mice were inhibitory. Administration of BCG further increased the suppressive activity of spleen cells in these T cell-deprived mice. From this evidence it appears that systemic administration of BCG activates natural suppressor cells in the bone marrow and elicits suppressor cells in the spleen through the migration and colonization of the spleen by bone marrow elements.

Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages

“…A TAM retention signal within hypoxic areas is delivered by SEMA3A through plexin A1/A4; conversely, NRP1 is downregulated in cancer, and its genetic inactivation in macrophages enhances TAM trapping within normoxic areas, resulting in the ablation of their immunosuppressive and proangiogenic activity (63). Partial correction of tumor hypoxia did not affect the relative distribution of TAM subsets or overall M2 marker expression, but rather downregulated the hypoxia-sensitive genes and proangiogenic activity of TAMs residing in the hypoxic areas (64).…”

Molecular Pathways: Targeting Tumor-Infiltrating Myeloid-Derived Suppressor Cells for Cancer Therapy

“…1). Indeed, extramedullar hemopoiesis (EMH) in reticuloendothelial and parenchymal tissues in cancer patients is well described (33)(34)(35), even if its role in MDSC accumulation is only partially known (36,37). Notably, when tumor cells are injected in adult non-tumor-bearing mice, having few splenic progenitors, hematopoietic progenitors mobilize from bone marrow, arrest, and accumulate in lymphoid and parenchymal organs other than in the tumors (38).…”

Delaying Bacillus Calmette-Guérin Vaccination from Birth to 4 1/2 Months of Age Reduces Postvaccination Th1 and IL-17 Responses but Leads to Comparable Mycobacterial Responses at 9 Months of Age

“…Indeed, it has long been recognized that suppressor responses can be induced by BCG vaccine (41,42). More recently, naturally occurring regulatory T cells (nTregs) (43) and IL-10 production (possibly by inducible adaptive Tregs) have been shown to play a role in immune suppression in mycobacterial infection (44)(45)(46)(47)(48).…”