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Purpose: This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma., Materials and Methods: Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed., Results: For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen-specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved., Conclusion: Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

We study the effects of the existence of another type of agents, called spies, in the minority game (MG). Unlike the normal agents in the MG, the spies do not carry any strategy. Instead, they decide their action by scouting some normal agents and take the minority action of the spied group. For a few spies and when there is useful information in the normal agents' actions, the spies can avoid the crowd effect of the normal agents and win more readily. When information becomes less useful and when more spies are present, the spies' crowd effect hurts the success rate of the spies themselves, and the normal agents could have a higher success rate than the spies. More spies actually assist more normal agents to win, as the spies also provide more winning quotas. This leads to a nonmonotonic behavior in the total success rate of the population as a function of the fraction of spies.