Table 1.

Impact of neutrophils and close relatives in cancer and TB.

	Tumor formation and evolution	Early Mtb infection and granuloma
Prognosis/Pathophysiology	• Clinical evidence (neutrophil to lymphocyte ratio) mostly links neutrophils to cancer progression. Poor prognosis. • Different granulocytic populations described with various functions. Anti-tumor activity of High Density Neutrophils (early stage tumor). Accumulation of immature neutrophils associated to cancer progression (Gr MDSCs or Low Density Neutrophils). Promote angiogenesis, tumor progression, and metastases (95) • In many cancers, different granulocyte subpopulations are described (96). Better definition is needed	• Early phase of infection: neutrophils contribute to innate resistance (11, 97) and granuloma formation (7, 98, 99) • Late phase of infection, active TB: established role of neutrophils to severe forms in preclinical models (8) and in humans (9) • Gr-MDSCs accumulate during early phase Mtb infection and active TB, in blood and lung in humans (31) • MDSCs may represent permissive reservoir for Mtb (34) and their accumulation associates with severe TB in mice (35)
Hypoxia and angiogenesis	• HIF-2α, selectively modulates neutrophil recruitment (100) • Neutrophil recruitment to early-stage tumors is linked to hypoxia (101) • Induction of angiogenic neutrophils in hypoxic conditions	• Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells (69) • Hif-1α increases NO production by neutrophils in early stage of Mm infection and is involved in control of bacterial growth (73) • Granuloma formation in the ZF model coincides with angiogenesis and local hypoxia (62)
Modulation of T cell response	• MDSCs are major players in tumor-mediated immunosuppression • Neutrophils in solid tumors are potent producers of Arg-1 and could contribute to local immune suppression (102, 103)	• MDSCs are present in lungs (3) but their role in development and evolution of granuloma remains unclear • Arg-1 is associated to severe TB in mouse models (104, 105) and is detected in necrotizing granulomas in humans (106). Pathway documented in MPs, however, deciphering neutrophil contribution to Arg-1 production would be of interest.
Tissue Remodeling	• MMP-9 delivered by tumor-recruited neutrophils is associated to tumor angiogenesis and dissemination (107) • Angiogenic neutrophils contribute to tumor growth and metastasis (108) • Neutrophils through COX-2-mediated PGE2 synthesis and elastase promote tumor cell proliferation (109)	• MMPs are involved in early granuloma formation and participate to tissue destruction during late phase (110, 111) • Pathogenic mycobacteria (Mm or Mtb) exploit the formation of new blood vessels to disseminate via MPs (62, 63). Neutrophils are migrating cells (112), their contribution to Mtb dissemination is not documented yet.