Cryoablation inhibition of distant untreated tumors (abscopal effect) is immune mediated.

Xueling Yang,Yongfei Guo,Zhi Guo,Wenwen Yu,Wenge Xing,Yan Wang,Tongguo Si

doi:10.18632/oncotarget.24105

Xueling Yang, Yongfei Guo + Show 5 more

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https://doi.org/10.18632/oncotarget.24105

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Abstract

Cryoablation is moderately effective against prostate cancer. Of note, the off-target or enlarged therapeutic effect after cryoablation is reported in routine clinical practice. To uncover it, we constructed a bilateral inguinal transplantation model of prostate cancer. All the mice were randomly subdivided into three groups: Group A (Control group), Group B (Surgery group), and Group C (Cryoablation group). All the procedures in three groups were conducted only for tumors in the target region (right groin). The tumors in untargeted region (left groin) received no treatment. We measured the growth of untargeted tumors and lung metastasis rate, and then explored the changes in a series of immune cells and danger signals. First, our results revealed the protective effect of cryoablation treatment against the abscopal tumor. The possible mechanism was mediated by an increase in the number of CD4+ T cells, CD8+ T cells, ratio T helper 1 (Th1)/Th2, the killing activity of cytotoxic T lymphocytes and NK cells. Hsp70 may be involved in the modulation of the immune response. The combination of weakened Ki67 activity and activated immune response delayed spectator tumor growth, decreased the pulmonary metastasis rate, and prolonged animal survival, with an inducible abscopal effect.

Highlights

Cryoablation is used in a variety of medical treatments with hollow needles through which cooled, thermally conductive fluids are circulated
To detect the possible abscopal effects induced by cryoablation, we designed one bilateral subcutaneous xenograft tumor model, in which tumors in the right groin were designated as the primary endpoint and treated, while tumors in the left groin were regarded as the abscopal group and were left untreated
Our study revealed the increasing trend of the spleen percentage of CD4+ T cells and CD8+ T cells, the T helper 1 (Th1)/ Th2 ratio, the killing activity of cytotoxic T lymphocytes (CTLs) after cryoablation on days 7 and 14 (P < 0.05), coupled with an increase of the spleen natural killer (NK) cell percentage in Group C (Cryoablation group), which suggested that cryoablation treatment can induce an antitumor immune response, which is mainly composed of CD8+ T cells, thereby inhibiting the growth of the untreated tumor, decreasing the rate of lung metastasis, and offering a survival benefit

Summary

Introduction

Cryoablation is used in a variety of medical treatments with hollow needles (cryoprobes) through which cooled, thermally conductive fluids are circulated. Cryoablation has been widely used against solid tumors in the lungs, liver, breast, kidneys, and prostate [1,2,3,4,5]. Evidence indicates that cryoablation is moderately effective, especially against early-stage prostate cancer [6, 7]. A rare clinical response is noticed in routine clinical practice, which is an off-target or enlarged therapeutic effect after cryoablation. Similar phenomena are well-recognized during other medical treatments, such as radiotherapy and gene therapy. In November 1992, Hatsumi Nagasawa and John www.oncotarget.com

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