肺癌免疫治疗假性进展的临床现状及研究进展
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摘要
目前肺癌的免疫治疗,尤其是免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的应用在晚期肺癌治疗中的地位正在逐渐提升。ICIs是通过对T细胞免疫抑制信号的解除来激活肿瘤患者的自身免疫系统。在临床治疗过程中,部分患者会出现一些非传统的临床反应,被认为是假性进展。目前对于肺癌假性进展的评估主要依据免疫影像学标准,同时许多研究者也致力于寻找血清学标志物或通过基因组测序来鉴别肿瘤假性进展和真进展。肺癌的假性进展表现多样,其临床评估和治疗目前存在诸多争议,虽然大多经过对症治疗后,患者症状可得到控制,且可继续进行下一疗程的免疫治疗,但仍然需要加强对假性进展的多方位了解,也有助于对临床免疫治疗策略提供更多可靠的依据。该文主要对肺癌免疫治疗假性进展的临床现状及研究进展进行综述。
The application of immunotherapy,especially with immune check point inhibitors(ICIs) in the treatment of advanced lung cancer is gradually rising. ICIs activate the immune system of cancer patients by blocking T cell immunosuppressive signals. In the course of clinical treatment,some patients will have some unconventional clinical reactions,which are considered as pseudoprogression. At present,the evaluation of pseudoprogression of lung cancer is mainly based on immunoimaging criteria. At the same time,serological markers or genome sequencing are used to differentiate pseudoprogression from true progression of lung cancer. Pseudoprogression of lung cancer is manifested variously,and there are still controversies about its clinical evaluation and treatment. Most of the clinical manifestations can be controlled and immunotherapy can be continued.To fully understanding the multi-dimensions of pseudoprogression will provide reliable basis for clinical immunotherapy strategies. In this article,the clinical manifestation and research progression of pseudoprogression in lung cancer patients undergoing immunotherapy are reviewed.
The application of immunotherapy,especially with immune check point inhibitors(ICIs) in the treatment of advanced lung cancer is gradually rising. ICIs activate the immune system of cancer patients by blocking T cell immunosuppressive signals. In the course of clinical treatment,some patients will have some unconventional clinical reactions,which are considered as pseudoprogression. At present,the evaluation of pseudoprogression of lung cancer is mainly based on immunoimaging criteria. At the same time,serological markers or genome sequencing are used to differentiate pseudoprogression from true progression of lung cancer. Pseudoprogression of lung cancer is manifested variously,and there are still controversies about its clinical evaluation and treatment. Most of the clinical manifestations can be controlled and immunotherapy can be continued.To fully understanding the multi-dimensions of pseudoprogression will provide reliable basis for clinical immunotherapy strategies. In this article,the clinical manifestation and research progression of pseudoprogression in lung cancer patients undergoing immunotherapy are reviewed.
引文
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[29]Asai M,Kato Y,Kawai S,et al.Management of cardiac tamponade during nivolumab of lung cancer with intrapericardial bleomycin:case report[J].Immunotherapy,2019.[Epub ahead of print]
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[31]Melian M,Lorente D,Aparici F,et al.Lung brain metastasis pseudoprogression after nivolumab and ipilimumab combination treatment[J].Thorac Cancer,2018,9(12):1770-1773.
[32]Fujimoto D,Yoshioka H,Kataoka Y,et al.Pseudoprogression in previously treated patients with non-small cell lung cancer who received nivolumab monotherapy[J].J Thorac Oncol,2018.[Epub ahead of print]
[33]Kim HK,Heo MH,Lee HS,et al.Comparison of RECISTto immune-related response criteria in patients with nonsmall cell lung cancer treated with immune-checkpoint inhibitors[J].Cancer Chemother Pharmacol,2017,80(3):591-598.
[34]Nishino M,Ramaiya NH,Chambers ES,et al.Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients[J].J Immunother Cancer,2016,4:84.
[2]Brahmer JR,Pardoll DM.Immune checkpoint inhibitors:making immunotherapy a reality for the treatment of lung cancer[J].Cancer Immunol Res,2013,1(2):85-91.
[3]Wolchok JD,Hoos A,O’Day S,et al.Guidelines for the evaluation of immune therapy activity in solid tumors:immune-related response criteria[J].Clin Cancer Res,2009,15(23):7412-7420.
[4]Li XY,Lyu TF,Song Y.New progress and confusion in immunotherapy of lung cancer[J].Chinese Journal of lung Disease(Electronic Edition),2018,11(6):647-653.[李欣颖,吕镗烽,宋勇.肺癌免疫治疗新进展及困惑[J].中华肺部疾病杂志(电子版),2018,11(6):647-653.]
[5]Chiou VL,Burotto M.Pseudoprogression and immune-related response in solid tumors[J].J Clin Oncol,2015,33(31):3541-3543.
[6]Eggermont AM,Kroemer G,Zitvogel L.Immunotherapy and the concept of a clinical cure[J].Eur J Cancer,2013,49(14):2965-2967.
[7]Chow LQ.Exploring novel immune-related toxicities and endpoints with immune-checkpoint inhibitors in non-small cell lung cancer[A].Am Soc Clin Oncol Educ Book[C].USA:ASCO,2013.
[8]Hamid O,Carvajal RD.Anti-programmed death-1 and anti-programmed death-ligand 1 antibodies in cancer therapy[J].Expert Opin Biol Ther,2013,13(6):847-861.
[9]Tanvetyanon T,Gray JE,Antonia SJ.PD-1 checkpoint blockade alone or combined PD-1 and CTLA-4 blockade as immunotherapy for lung cancer?[J].Expert Opin Biol Ther,2017,17(3):305-312.
[10]Hellmann MD,Ciuleanu TE,Pluzanski A,et al.Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden[J].N Engl J Med,2018,378(22):2093-2104.
[11]Ishida M,Iwai Y,Tanaka Y,et al.Differential expression of PD-L1 and PD-L2,ligands for an inhibitory receptor PD-1,in the cells of lymphohematopoietic tissues[J].Immunol Lett,2002,84(1):57-62.
[12]Lin C,Cheng X,Liu JN,et al.Advances of PD-1/PD-L1signaling pathway in immune escape and treatment for non-small cell lung cancer[J].Chinese Journal of Lung Cancer,2014,17(10):734-740.[林城,陈雄,刘静南,等PD-1/PD-L1信号通路在非小细胞肺癌免疫逃逸及其治疗中的研究进展[J].中国肺癌杂志,2014,17(10):734-740.]
[13]Nadal E,Massuti B,Domine M,et al.Immunotherapy with checkpoint inhibitors in non-small cell lung cancer:insights from long-term survivors[J].Cancer Immunol Immunother,2019.[Epub ahead of print]
[14]Verma V,Sharma G,Singh A.Immunotherapy in extensive small cell lung cancer[J].Exp Hematol Oncol,2019,8:5.
[15]Calles A,Aguado G,Sandoval C,et al.The role of immunotherapy in small cell lung cancer[J].Clin Transl Oncol,2019.[Epub ahead of print]
[16]Wang Q,Gao J,Wu X.Pseudoprogression and hyperprogression after checkpoint blockade[J].Int Immunopharmacol,2018,58:125-135.
[17]Carter BW,Halpenny DF,Ginsberg MS,et al.Immunotherapy in non-small cell lung cancer treatment:current status and the role of imaging[J].J Thorac Imaging,2017,32(5):300-312.
[18]Katz SI,Hammer M,Bagley SJ,et al.Radiologic pseudoprogression during anti-PD-1 therapy for advanced nonsmall cell lung cancer[J].J Thorac Oncol,2018,13(7):978-986.
[19]Vrankar M,Unk M.Immune RECIST criteria and symptomatic pseudoprogression in non-small cell lung cancer patients treated with immunotherapy[J].Radiol Oncol,2018,52(4):365-369.
[20]Guibert N,Mazieres J,Delaunay M,et al.Monitoring of KRAS-mutated ctDNA to discriminate pseudo-progression from true progression during anti-PD-1 treatment of lung adenocarcinoma[J].Oncotarget,2017,8(23):38056-38060.
[21]Matsuo N,Azuma K,Hattori S,et al.Association between soluble immune mediators and tumor responses in patients with nonsmall cell lung cancer treated with anti-PD-1 inhibitor[J].Int J Cancer,2019,144(5):1170-1179.
[22]Zer A,Sung MR,Walia P,et al.Correlation of neutrophil to lymphocyte ratio and absolute neutrophil count with outcomes with PD-1 axis inhibitors in patients with advanced non-small-cell lung cancer[J].Clin Lung Cancer,2018,19(5):426-434.
[23]Jensen TJ,Goodman AM,Kato S,et al.Genome-wide sequencing of cell-free DNA identifies copy-number alterations that can be used for monitoring response to immunotherapy in cancer patients[J].Mol Cancer Ther,2019,18(2):448-458.
[24]Hammer M,Bagley S,Aggarwal C,et al.Thoracic imaging of non-small cell lung cancer treated with anti-programmed death receptor-1 therapy[J].Curr Probl Diagn Radiol,2019,48(2):142-147.
[25]Kato R,Hayashi H,Tanizaki J,et al.Peritumoural groundglass opacity associated with tumour pseudoprogression in a patient with non-small cell lung cancer treated with nivolumab[J].ESMO Open,2017,2(1):e000145.
[26]Li J,Li CY,Xiong YL.,et al.Case analysis about the influence of TMB to immunotherapy in NSCLC[J].Journal of Modern Medicine&Health,2018,34(14):2116-2118.[李娟,李崇义,熊艳丽,等.基于TMB对肺癌免疫治疗病例分析[J].现代医药卫生,2018,34(14):2116-2118.]
[27]Kolla BC,Patel MR.Recurrent pleural effusions and cardiac tamponade as possible manifestations of pseudoprogression associated with nivolumab therapy-a report of two cases[J].J Immunother Cancer,2016,4:80.
[28]Yamasaki M,Daido W,Saito N,et al.Pericardial effusion with tamponade in lung cancer patients during treatment with nivolumab:a report of two cases[J].Front Oncol,2019,9:4.
[29]Asai M,Kato Y,Kawai S,et al.Management of cardiac tamponade during nivolumab of lung cancer with intrapericardial bleomycin:case report[J].Immunotherapy,2019.[Epub ahead of print]
[30]Liu G,Chen T,Li R,et al.Well-controlled pleural effusion indicated pseudoprogression after immunotherapy in lung cancer:a case report[J].Thorac Cancer,2018,9(9):1190-1193.
[31]Melian M,Lorente D,Aparici F,et al.Lung brain metastasis pseudoprogression after nivolumab and ipilimumab combination treatment[J].Thorac Cancer,2018,9(12):1770-1773.
[32]Fujimoto D,Yoshioka H,Kataoka Y,et al.Pseudoprogression in previously treated patients with non-small cell lung cancer who received nivolumab monotherapy[J].J Thorac Oncol,2018.[Epub ahead of print]
[33]Kim HK,Heo MH,Lee HS,et al.Comparison of RECISTto immune-related response criteria in patients with nonsmall cell lung cancer treated with immune-checkpoint inhibitors[J].Cancer Chemother Pharmacol,2017,80(3):591-598.
[34]Nishino M,Ramaiya NH,Chambers ES,et al.Immune-related response assessment during PD-1 inhibitor therapy in advanced non-small-cell lung cancer patients[J].J Immunother Cancer,2016,4:84.