Modulation of Macrophage Function by Oral Squamous Cell Carcinoma Cells

Objectives: Macrophages play a complex role in pathogenesis of oral squamous cell carcinoma (OSCC); M1 macrophages are associated with anti-tumour activity, whereas M2 macrophages support tumour progression. These cells are highly plastic however, and their effector functions can be modulated in response to locally derived stimuli. Such stimuli may originate from tumour cells themselves or from microflora inhabiting the oral mucosa, e.g. Porphyromonas gingivalis (Pg). Having previously characterised M1 and M2 inflammatory responses to Pg, the present study first investigated whether tumour-derived factors affected polarisation into M1 and M2 phenotypes, and secondly whether these factors modulated the responses of M1 and M2 macrophages to Pg LPS. 

Methods: In the presence or absence of conditioned media (CM) from the established OSCC cell line H357, THP-1 (human leukaemia derived monocytic) cells were treated with PMA, PMA + IFNγ or PMA + IL-4 to generate differentiated but non-polarised, M1, and M2 macrophages, respectively. Cells were then washed and stimulated for 24 hours with LPS. Inflammatory cytokines TNFα, IL-1β and IL-6 were assayed by ELISA. Macrophage cell number and viability were measured using Trypan blue exclusion.

Results: Macrophages treated with H357 CM retained their M1 and M2 inflammatory profiles, but in response to LPS, IL-1β and IL-6 production was significantly amplified. TNFα production was unaffected. Furthermore, CM modulated macrophage cell numbers.  

Conclusion: H357 CM did not affect THP-1 cell polarisation into M1 or M2, but did modulate M1 and M2 responses to LPS by amplifying cytokine production. In addition, oral squamous cell carcinoma cells may modulate macrophage cell numbers. Thus, complex interactions between oral bacteria, macrophages and carcinoma cells may have a role in the facilitation of tumour progression.