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. 2021 Mar 5;40:89. doi: 10.1186/s13046-021-01883-0

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Wtp53 and high-dose delivery contribute to the Abscopal effect in in vivo NSCLC tumor models. a Experimental design of in vivo experiments aimed at evaluating the tumor-growth of irradiated (IR) and non-irradiated contralateral (NIR) tumors; control (UnIR) non-irradiated mice are also shown. b WTp53 A549 xenografts and (c) p53-null H1299 xenografts. Wtp53-depleted (sh/p53) (d) and control (sh/scr) (e) A549 xenograft tumor growth after RT are reported. Volumetric data were obtained using 8 mice/group and were normalized to the initial volume of tumor-bearing mice at the time of radiation (V0). Data represent the mean (± standard deviation, SD) of two independent experiments. (* p < 0.05; **p < 0.01). f Representative images of the abscopal effect in mice bearing functional p53 (A549 sh/scr). The mice bearing silenced p53 (A549 sh/p53) showed, as expected, tumor growth in the NIR contralateral mass. All the animals were xenografted subcutaneously on both flanks. Black arrows show tumors directly irradiated (20 Gy). g Immunohistochemical staining for F4/80 in mouse A549 xenograft tissue section. Images are representative of control (UnIR), 20 Gy-irradiated (IR) and contralateral non-irradiated (NIR) tumor masses infiltrated by F4/80-positive macrophages (arrow). The number of positive cells in 6 random field profiles was used for statistical analysis. h Lipofuscin staining of A549 xenograft tissue section to detect senescence cells. To quantify lipofuscin positive cells, a homemade Matlab tool was used. The appropriated mask needed to identify the lipofuscin positive cells in the investigated area was obtained using the function imageSegmenter as detailed in supplementary notes. (*** p < 0.0001) (i) IL6 expression through digital qRT-PCR analysis of RNA extracted from A549 xenograft tissue sections. j Different expression levels of IL6 in serum collected from A549 xenograft nude mice irradiated (IR) or not (UnIR) at 20 Gy. (* p < 0.05; ***p < 0.001)