Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy.

Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells. LDRT elicited predominantly CD4 <sup>+</sup> cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4 <sup>+</sup> cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell-infiltrated tumors. SIGNIFICANCE: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4 <sup>+</sup> effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors.This article is highlighted in the In This Issue feature, p. 1

Oiling accelerates loss of salt marshes, southeastern Louisiana

The 2010 BP Deepwater Horizon (DWH) oil spill damaged thousands of km2 of intertidal marsh along shorelines that had been experiencing elevated rates of erosion for decades. Yet, the contribution of marsh oiling to landscape-scale degradation and subsequent land loss has been difficult to quantify. Here, we applied advanced remote sensing techniques to map changes in marsh land cover and open water before and after oiling. We segmented the marsh shorelines into non-oiled and oiled reaches and calculated the land loss rates for each 10% increase in oil cover (e.g. 0% to >70%), to determine if land loss rates for each reach oiling category were significantly different before and after oiling. Finally, we calculated background land-loss rates to separate natural and oil-related erosion and land loss. Oiling caused significant increases in land losses, particularly along reaches of heavy oiling (>20% oil cover). For reaches with ≥20% oiling, land loss rates increased abruptly during the 2010-2013 period, and the loss rates during this period are significantly different from both the pre-oiling (p < 0.0001) and 2013-2016 post-oiling periods (p < 0.0001). The pre-oiling and 2013-2016 post-oiling periods exhibit no significant differences in land loss rates across oiled and non-oiled reaches (p = 0.557). We conclude that oiling increased land loss by more than 50%, but that land loss rates returned to background levels within 3-6 years after oiling, suggesting that oiling results in a large but temporary increase in land loss rates along the shoreline