Cryoablation of primary breast cancer tumors induces a systemic abscopal effect altering TIME (Tumor Immune Microenvironment) in distant tumors

原发性乳腺癌肿瘤冷冻消融可引起全身远隔效应,从而改变远处肿瘤的 TIME(肿瘤免疫微环境)

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作者:Flávia Sardela de Miranda, Dalia Martinez-Marin, Rachel L Babcock, Maribel Castro, Geetha P Boligala, Sonia Y Khan, Kathryn L Furr, Isabel Castro-Piedras, Nicholas Wagner, Dakota E Robison, Karla Daniele, Sharda P Singh, Kevin Pruitt, Michael W Melkus, Rakhshanda Layeequr Rahman

Conclusions

These results better define the early mechanisms through which cryoablation improves tumor elimination, which is mediated by enhanced frequencies of anti-tumoral cells such as NK and cDC1s at the abscopal tumor and in the spleen of mice treated with cryoablation, respectively.

Methods

One million 4T1-12B-luciferase expressing cells were transplanted into the mammary fat pad of BALB/c mice. Two weeks later, left (primary) tumors were either resected or cryoablated. A week after the procedure, right (abscopal) and left tumors, along with spleen, tumor-draining lymph node and blood were collected and processed for flow cytometry and/or RNA-sequencing and immunofluorescence.

Results

Here we show that cryoablation of mouse mammary carcinomas results in smaller abscopal tumors that harbor increased frequencies of anti-tumor cells [such as natural killer (NK) cells], accompanied by a systemic increase in the frequency of migratory conventional type 1 dendritic cells (cDC1; CD103+ XCR1+), compared to resection. The changes in cell frequencies are mirrored by the immune gene signature of the abscopal tumors, with cryoablation inducing genes involved with NK cell activation and leukocyte-mediated toxicity, including IL11ra1 and Pfr1. Conclusions: These results better define the early mechanisms through which cryoablation improves tumor elimination, which is mediated by enhanced frequencies of anti-tumoral cells such as NK and cDC1s at the abscopal tumor and in the spleen of mice treated with cryoablation, respectively.

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