远隔效应的作用机制及临床进展
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摘要
随着远隔效应概念的提出及放疗技术的发展,越来越多关于如何促进远隔效应的临床前及临床试验投入研究。近年来,有研究指出,放疗联合免疫治疗可促进原发及转移部位肿瘤消退。同步智能技术的发展,如纳米颗粒技术、SRBs及肿瘤内输送技术,放疗联合免疫治疗有望增强肿瘤免疫原性、减轻肿瘤免疫抑制及剂量限制性毒性作用。
Abatract: With the introduction of the concept of distant effects and the development of radiotherapy technology,more and more researches on how to promote remote clinical and clinical trials have been carried out. In recent years,studies have shown that radiotherapy combined with immunotherapy can promote tumor regression in primary and metastatic sites. The development of synchronous intelligent technology,such as nano particle technology,SRBs and intratumoral delivery technology,is expected to enhance the immunogenicity of tumor,reduce the immunosuppression of tumor and the dose restrictive toxicity.
Abatract: With the introduction of the concept of distant effects and the development of radiotherapy technology,more and more researches on how to promote remote clinical and clinical trials have been carried out. In recent years,studies have shown that radiotherapy combined with immunotherapy can promote tumor regression in primary and metastatic sites. The development of synchronous intelligent technology,such as nano particle technology,SRBs and intratumoral delivery technology,is expected to enhance the immunogenicity of tumor,reduce the immunosuppression of tumor and the dose restrictive toxicity.
引文
[1]Mole RH.Whole body irradiation;radiobiology or medicine?[J].Br J Radiol,1953,26(305):234-241.
[2]Ehlers G,Fridman M.Abscopal effect of radiation in papillary adenocarcinoma[J].Br J Radiol,1973,46(543):220-222.
[3]Kingsley DP.An interesting case of possible abscopal effect in malignant melanoma[J].Br J Radiol,1975,48(574):863-866.
[4]Demaria S,Ng B,Devitt ML,et al.Ionizing radiation inhibition of distant untreated tumors(abscopal effect)is immune mediated[J].Int J Radiat Oncol Biol Phys,2004,58(3):862-870.
[5]Golden EB,Chhabra A,Chachoua A,et al.Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours:a proof-of-principle trial[J].Lancet Oncol,2015,16(7):795-803.
[6]Twyman-Saint VC,Rech AJ,Maity A,et al.Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer[J].Nature,2015,520(7547):373-377.
[7]Grass GD,Krishna N,Kim S.The immune mechanisms of abscopal effect in radiation therapy[J].Curr Probl Cancer,2016,40(1):10-24.
[8]Barker HE,Paget JT,Khan AA,et al.The tumour microenvironment after radiotherapy:mechanisms of resistance and recurrence[J].Nat Rev Cancer,2015,15(7):409-425.
[9]Vatner RE,Cooper BT,Vanpouille-Box C,et al.Combinations of immunotherapy and radiation in cancer therapy[J].Front Oncol,2014,4:325.
[10]Habets TH,Oth T,Houben AW,et al.Fractionated radiotherapy with 3×8 Gy induces systemic anti-Tumour responses and abscopal tumour inhibition without modulating the humoral anti-tumour response[J].PLoS One,2016,11(7):e159515.
[11]Deng L,Liang H,Burnette B,et al.Irradiation and antiPD-L1 treatment synergistically promote antitumor immunity in mice[J].J Clin Invest,2014,124(2):687-695.
[12]Vanpouille-Box C,Alard A,Aryankalayil MJ,et al.DNAexonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity[J].Nat Commun,2017,8:15618.
[13]Young KH,Baird JR,Savage T,et al.Optimizing timing of immunotherapy improves control of tumors by hypofractionated radiation therapy[J].PLoS One,2016,11(6):e157164.
[14]Kang J,Demaria S,Formenti S.Current clinical trials testing the combination of immunotherapy with radiotherapy[J].J Immunother Cancer,2016,4:51.
[15]McNamee EN,Korns JD,Homann D,et al.Hypoxia and hypoxia-inducible factors as regulators of T cell development,differentiation,and function[J].Immunol Res,2013,55(1-3):58-70.
[16]Hams E,Saunders SP,Cummins EP,et al.The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10production by B1 cells[J].Shock,2011,36(3):295-302.
[17]Gorin JB,Menager J,Gouard S,et al.Antitumor immunity induced after alpha irradiation[J].Neoplasia,2014,16(4):319-328.
[18]Zheng W,Skowron KB,Namm JP,et al.Combination of radiotherapy and vaccination overcomes checkpoint blockade resistance[J].Oncotarget,2016,7(28):43039-43051.
[19]Dranoff G,Jaffee E,Lazenby A,et al.Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent,specific,and long-lasting anti-tumor immunity[J].Proc Natl Acad Sci U S A,1993,90(8):3539-3543.
[20]Li SY,Liu Y,Xu CF,et al.Restoring anti-tumor functions of T cells via nanoparticle-mediated immune checkpoint modulation[J].J Control Release,2016,231:17-28.
[21]Ngwa W,Kumar R,Sridhar S,et al.Targeted radiotherapy with gold nanoparticles:current status and future perspectives[J].Nanomedicine(Lond),2014,9(7):1063-1082.
[22]Kim MS,Lee EJ,Kim JW,et al.Gold nanoparticles enhance anti-tumor effect of radiotherapy to hypoxic tumor[J].Radiat Oncol J,2016,34(3):230-238.
[23]Detappe A,Kunjachan S,Rottmann J,et al.AGuIXnanoparticles as a promising platform for image-guided radiation therapy[J].Cancer Nanotechnol,2015,6(1):4.
[24]Ngwa W,Boateng F,Kumar R,et al.Smart radiation therapy biomaterials[J].Int J Radiat Oncol Biol Phys,2017,97(3):624-637.
[25]DeMuth PC,Li AV,Abbink P,et al.Vaccine delivery with microneedle skin patches in nonhuman primates[J].Nat Biotechnol,2013,31(12):1082-1085.
[26]Dranoff G.Experimental mouse tumour models:what can be learnt about human cancer immunology?[J].Nat Rev Immunol,2011,12(1):61-66.
[27]Park J,Gerber MH,Babensee JE.Phenotype and polarization of autologous T cells by biomaterial-treated dendritic cells[J].J Biomed Mater Res A,2015,103(1):170-184.
[28]Bennewitz NL,Babensee JE.The effect of the physical form of poly(lactic-co-glycolic acid)carriers on the humoral immune response to co-delivered antigen[J].Biomaterials,2005,26(16):2991-2999.
[29]Ng SY,Colborn KL,Cambridge L,et al.Acute toxicity with intensity modulated radiotherapy versus 3-dimensional conformal radiotherapy during preoperative chemoradiation for locally advanced rectal cancer[J].Radiother Oncol,2016,121(2):252-257.
[30]Rodriguez-Ruiz ME,Rodriguez I,Barbes B,et al.Brachytherapy attains abscopal effects when combined with immunostimulatory monoclonal antibodies[J].Brachytherapy,2017,16(6):1246-1251.
[31]Marabelle A,Kohrt H,Sagiv-Barfi I,et al.Depleting tumor-specific Tregs at a single site eradicates disseminated tumors[J].J Clin Invest,2013,123(6):2447-2463.
[32]Toy R,Roy K.Engineering nanoparticles to overcome barriers to immunotherapy[J].Bioeng Transl Med,2016,1(1):47-62.
[33]Fransen MF,Sluijter M,Morreau H,et al.Local activation of CD8 T cells and systemic tumor eradication without toxicity via slow release and local delivery of agonistic CD40 antibody[J].Clin Cancer Res,2011,17(8):2270-2280.
[34]Ngwa W,Irabor OC,Schoenfeld JD,et al.Using immunotherapy to boost the abscopal effect[J].Nat Rev Cancer,2018,18(5):313-322.
[2]Ehlers G,Fridman M.Abscopal effect of radiation in papillary adenocarcinoma[J].Br J Radiol,1973,46(543):220-222.
[3]Kingsley DP.An interesting case of possible abscopal effect in malignant melanoma[J].Br J Radiol,1975,48(574):863-866.
[4]Demaria S,Ng B,Devitt ML,et al.Ionizing radiation inhibition of distant untreated tumors(abscopal effect)is immune mediated[J].Int J Radiat Oncol Biol Phys,2004,58(3):862-870.
[5]Golden EB,Chhabra A,Chachoua A,et al.Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours:a proof-of-principle trial[J].Lancet Oncol,2015,16(7):795-803.
[6]Twyman-Saint VC,Rech AJ,Maity A,et al.Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer[J].Nature,2015,520(7547):373-377.
[7]Grass GD,Krishna N,Kim S.The immune mechanisms of abscopal effect in radiation therapy[J].Curr Probl Cancer,2016,40(1):10-24.
[8]Barker HE,Paget JT,Khan AA,et al.The tumour microenvironment after radiotherapy:mechanisms of resistance and recurrence[J].Nat Rev Cancer,2015,15(7):409-425.
[9]Vatner RE,Cooper BT,Vanpouille-Box C,et al.Combinations of immunotherapy and radiation in cancer therapy[J].Front Oncol,2014,4:325.
[10]Habets TH,Oth T,Houben AW,et al.Fractionated radiotherapy with 3×8 Gy induces systemic anti-Tumour responses and abscopal tumour inhibition without modulating the humoral anti-tumour response[J].PLoS One,2016,11(7):e159515.
[11]Deng L,Liang H,Burnette B,et al.Irradiation and antiPD-L1 treatment synergistically promote antitumor immunity in mice[J].J Clin Invest,2014,124(2):687-695.
[12]Vanpouille-Box C,Alard A,Aryankalayil MJ,et al.DNAexonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity[J].Nat Commun,2017,8:15618.
[13]Young KH,Baird JR,Savage T,et al.Optimizing timing of immunotherapy improves control of tumors by hypofractionated radiation therapy[J].PLoS One,2016,11(6):e157164.
[14]Kang J,Demaria S,Formenti S.Current clinical trials testing the combination of immunotherapy with radiotherapy[J].J Immunother Cancer,2016,4:51.
[15]McNamee EN,Korns JD,Homann D,et al.Hypoxia and hypoxia-inducible factors as regulators of T cell development,differentiation,and function[J].Immunol Res,2013,55(1-3):58-70.
[16]Hams E,Saunders SP,Cummins EP,et al.The hydroxylase inhibitor dimethyloxallyl glycine attenuates endotoxic shock via alternative activation of macrophages and IL-10production by B1 cells[J].Shock,2011,36(3):295-302.
[17]Gorin JB,Menager J,Gouard S,et al.Antitumor immunity induced after alpha irradiation[J].Neoplasia,2014,16(4):319-328.
[18]Zheng W,Skowron KB,Namm JP,et al.Combination of radiotherapy and vaccination overcomes checkpoint blockade resistance[J].Oncotarget,2016,7(28):43039-43051.
[19]Dranoff G,Jaffee E,Lazenby A,et al.Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent,specific,and long-lasting anti-tumor immunity[J].Proc Natl Acad Sci U S A,1993,90(8):3539-3543.
[20]Li SY,Liu Y,Xu CF,et al.Restoring anti-tumor functions of T cells via nanoparticle-mediated immune checkpoint modulation[J].J Control Release,2016,231:17-28.
[21]Ngwa W,Kumar R,Sridhar S,et al.Targeted radiotherapy with gold nanoparticles:current status and future perspectives[J].Nanomedicine(Lond),2014,9(7):1063-1082.
[22]Kim MS,Lee EJ,Kim JW,et al.Gold nanoparticles enhance anti-tumor effect of radiotherapy to hypoxic tumor[J].Radiat Oncol J,2016,34(3):230-238.
[23]Detappe A,Kunjachan S,Rottmann J,et al.AGuIXnanoparticles as a promising platform for image-guided radiation therapy[J].Cancer Nanotechnol,2015,6(1):4.
[24]Ngwa W,Boateng F,Kumar R,et al.Smart radiation therapy biomaterials[J].Int J Radiat Oncol Biol Phys,2017,97(3):624-637.
[25]DeMuth PC,Li AV,Abbink P,et al.Vaccine delivery with microneedle skin patches in nonhuman primates[J].Nat Biotechnol,2013,31(12):1082-1085.
[26]Dranoff G.Experimental mouse tumour models:what can be learnt about human cancer immunology?[J].Nat Rev Immunol,2011,12(1):61-66.
[27]Park J,Gerber MH,Babensee JE.Phenotype and polarization of autologous T cells by biomaterial-treated dendritic cells[J].J Biomed Mater Res A,2015,103(1):170-184.
[28]Bennewitz NL,Babensee JE.The effect of the physical form of poly(lactic-co-glycolic acid)carriers on the humoral immune response to co-delivered antigen[J].Biomaterials,2005,26(16):2991-2999.
[29]Ng SY,Colborn KL,Cambridge L,et al.Acute toxicity with intensity modulated radiotherapy versus 3-dimensional conformal radiotherapy during preoperative chemoradiation for locally advanced rectal cancer[J].Radiother Oncol,2016,121(2):252-257.
[30]Rodriguez-Ruiz ME,Rodriguez I,Barbes B,et al.Brachytherapy attains abscopal effects when combined with immunostimulatory monoclonal antibodies[J].Brachytherapy,2017,16(6):1246-1251.
[31]Marabelle A,Kohrt H,Sagiv-Barfi I,et al.Depleting tumor-specific Tregs at a single site eradicates disseminated tumors[J].J Clin Invest,2013,123(6):2447-2463.
[32]Toy R,Roy K.Engineering nanoparticles to overcome barriers to immunotherapy[J].Bioeng Transl Med,2016,1(1):47-62.
[33]Fransen MF,Sluijter M,Morreau H,et al.Local activation of CD8 T cells and systemic tumor eradication without toxicity via slow release and local delivery of agonistic CD40 antibody[J].Clin Cancer Res,2011,17(8):2270-2280.
[34]Ngwa W,Irabor OC,Schoenfeld JD,et al.Using immunotherapy to boost the abscopal effect[J].Nat Rev Cancer,2018,18(5):313-322.