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Millet, R.

Publications and source records attributed to Millet, R..

2 recordsLinked to original sources

The effect of non-linear competitive interactions on quantifying niche and fitness differences

The niche and fitness differences of modern coexistence theory separate mechanisms into stabilizing and equalizing components. Although this decomposition can help us predict and understand species coexistence, the extent to which mechanistic inference is sensitive to the method used to partition niche and fitness differences remains unclear. We apply two alternative methods to assess niche and fitness differences to four well known community models. We show that because standard methods based on linear approximations do not capture the full community dynamics, they can sometimes lead to incorrect predictions of coexistence and misleading interpretations of stabilizing and equalizing mechanisms. Conversely, a more recently developed method to decompose niche and fitness differences, that accounts for the full nonlinear dynamics of competition, consistently identifies the correct contribution of stabilizing and equalizing components. This approach further reveals that when the true complexity of the system is taken into account, essentially all mechanisms comprise both stabilizing and equalizing components. Amidst growing interest in the role of non-additive and higher-order interactions in regulating species coexistence, we propose that the effective decomposition of niche and fitness differences will become increasingly reliant on methods that account for the inherent non-linearity of community dynamics.

ecology

Small-molecule P2RX7 activator sensitizes tumor to immunotherapy and vaccinates mouse against tumor re-challenge

Only a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop new therapeutic strategies to improve patient outcome. We developed a new chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates PD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7 expressing cells to generate IL-18 which leads to the production of IFN-{gamma} by Natural Killer and CD4+ T cells within tumors. Combined with immune checkpoint inhibitor, the molecule induces a complete tumor regression in 80% of LLC tumor bearing mice. Cured mice are also protected against tumor re-challenge due to a CD8-dependent protective response. Hence, combination treatment of small-molecule P2RX7 activator followed by immune checkpoint inhibitor represents a promising novel strategy that may be active against NSCLC.

cancer biology