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摘要:
近年来，非小细胞肺癌（non-small cell lung cancer, NSCLC）患者的生存率因手术、放疗、化疗及靶向治疗等各方面治疗的进展而均取得了很大的进展，但NSCLC患者总的5年生存率仍然不理想。免疫治疗利用免疫系统来控制、杀灭和清除肿瘤细胞，已成为肿瘤治疗的一种重要手段。肿瘤免疫学和分子生物学等各方面的最新进展，不仅推动了免疫治疗中非抗原特异性治疗的发展，比如，以T淋巴细胞的免疫检查点为靶点的单克隆抗体，还推动了抗原特异性免疫治疗或者说是疫苗方面的发展，使得免疫治疗成为十分有前景的治疗方式。这里仅对NSCLC的疫苗治疗最新研究进展进行综述。
Abstract:In recent years, the total 5-year survival rate of the patients with non-small cell lung cancer (NSCLC) remains unsatisfactory, though there are some recent advances in the survival rate of the patients with NSCLC because of the advances in surgery, irradiation, chemotherapy and targeted therapy. The immunotherapy which utilizes the immune system to control, kill and eradicate cancer cell is a viable treatment approach for cancer. Recent advances in our understanding of cancer immunology and molecular biology resulted in the development of non-antigen specific immunotherapy, for example, monoclonal antibodies targeting immune checkpoints on the T-cell lymphocyte. Not only non-antigen specific immunotherapy, but also the antigen specific immunotherapy or vaccination have made great progress. This makes them become promising therapeutic agents. Herein, we review the recent progress and advances of tumor vaccine from randomized controlled trials.
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Key words:
- Non-small cell lung cancer /
- Immunotherapy /
- Vaccine
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[1] Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2015[J]. CA Cancer J Clin, 2015, 65(1): 5-29 doi: 10.3322/caac.21254
[1] Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2015[J]. CA Cancer J Clin, 2015, 65(1): 5-29 [2] Herbst RS, Heymach JV, Lippman SM. Lung cancer[J]. N Engl J Med, 2008, 359(13): 1367-80. [2] Herbst RS, Heymach JV, Lippman SM. Lung cancer[J]. N Engl J Med, 2008, 359(13): 1367-80. doi: 10.1056/NEJMra0802714
[3] Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small cell lung cancer[J]. N Engl J Med, 2010, 363(18): 1693-703. doi: 10.1056/NEJMoa1006448
[3] Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in non-small cell lung cancer[J]. N Engl J Med, 20 10, 363(18): 1693-703. [4] Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR[J]. N Engl J Med, 2010, 362(25): 2380-8. [4] Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR[J]. N Engl J Med, 2010, 362(25): 2380-8. doi: 10.1056/NEJMoa0909530
[5] Pardoll D. Does the immune system see tumors as foreign or self?[J]. Annu Rev Immunol, 2003, 21: 807-39. doi: 10.1146/annurev.immunol.21.120601.141135
[5] Pardoll D. Does the immune system see tumors as foreign or self?[J]. Annu Rev Immunol, 2003, 21: 807-39. [6] Ribas A, Butterfield LH, Glaspy JA, et al. Current developments in cancer vaccines and cellular immunotherapy[J]. J Clin Oncol, 20 03, 21(12): 2415-32. [6] Ribas A, Butterfield LH, Glaspy JA, et al. Current developments in cancer vaccines and cellular immunotherapy[J]. J Clin Oncol, 2003, 21(12): 2415-32. doi: 10.1200/JCO.2003.06.041
[7] Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance[J]. Nat Rev Cancer, 2005, 5(4): 263-74. doi: 10.1038/nrc1586
[7] Zou W. Immunosuppressive networks in the tumour environment and their therapeutic relevance[J]. Nat Rev Cancer, 2005, 5(4): 26 3-74. [8] Decoster L, Wauters I, Vansteenkiste JF. Vaccination therapy for non-small-cell lung cancer: review of agents in phase Ⅲ development[J]. Ann Oncol, 2012, 23(6): 1387-93. [8] Decoster L, Wauters I, Vansteenkiste JF. Vaccination therapy for non-small-cell lung cancer: review of agents in phase Ⅲdevelopment[J]. Ann Oncol, 2012, 23(6): 1387-93. doi: 10.1093/annonc/mdr564
[9] Gure AO, Chua R, Williamson B, et al. Cancer-testis genes are coordinately expressed and are markers of poor outcome in nonsmall- cell lung cancer[J]. Clin Cancer Res, 2005, 11(22): 8055-62. [9] Gure AO, Chua R, Williamson B, et al. Cancer-testis genes are coordinately expressed and are markers of poor outcome in non-small-cell lung cancer[J]. Clin Cancer Res, 2005, 11(22): 8055-62. doi: 10.1158/1078-0432.CCR-05-1203
[10] 刘庆伦, 张昌卿, 马凯涛. 非小细胞肺癌MAGE-3基因产物的表达[J]. 中华肿瘤杂志, 2000, 22(2): 138-40. http://www.cnki.com.cn/Article/CJFDTOTAL-ZHZL200002021.htm Liu QL, Zhang CQ, Ma KT. Expression of MAGE-3 gene product in non-small cell lung cancer[J]. Zhonghua Zhong Liu Za Zhi, 2000, 22(2): 138-40. http://www.cnki.com.cn/Article/CJFDTOTAL-ZHZL200002021.htm
[10] 刘庆伦, 张昌卿, 马凯涛. 非小细胞肺癌MAGE-3基因产物的 表达[J] 中华肿瘤杂志, 2000, 22(2): 138-40. [Liu QL, Zhang CQ, Ma KT. Expression of MAGE-3 gene product in non-small cell lung cancer[J]. Zhonghua Zhong Liu Za Zhi, 2000, 22(2): 13 8-40.] [11] Vansteenkiste J, Zielinski M, Linder A, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase Ⅱ randomized study results[J]. J Clin Oncol, 2013, 31(19): 23 96-403. [11] Vansteenkiste J, Zielinski M, Linder A, et al. Adjuvant MAGE-A3 immunotherapy in resected non-small-cell lung cancer: phase Ⅱ randomized study results[J]. J Clin Oncol, 2013, 31(19): 2396-403. doi: 10.1200/JCO.2012.43.7103
[12] Ulloa-Montoya F, Louahed J, Dizier B, et al. Predictive gene signaturein MAGEA3 antigen-specific cancer immunotherapy[J]. J Clin Oncol, 2013, 31(19): 2388-95. doi: 10.1200/JCO.2012.44.3762
[12] Ulloa-Montoya F, Louahed J, Dizier B, et al. Predictive gene signaturein MAGEA3 antigen-specific cancer immunotherapy[J]. J Clin Oncol, 2013, 31(19): 2388-95. [13] Vansteenkiste JF, Cho, B, Vanakesa, T, et al. MAGRIT, a double blind, randomized, placebo-controlled phase Ⅲ study to assess the efficacy of the recMAGE-A3+ AS15 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small cell lung cancer (NSCLC)[J]. Ann Oncol, 2014, 25(Suppl 4): iv409-16.
[13] Vansteenkiste JF, Cho, B, Vanakesa, T, et al. MAGRIT, a double blind, randomized, placebo-controlled phase Ⅲ study to assess the efficacy of the recMAGE-A3+ AS15 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small cell lung cancer (NSCLC)[J]. Ann Oncol, 2014, 25 (Suppl 4): iv409-16. [14] Vlad AM, Kettel JC, Alajez NM, et al. MUC1 immunobiology: from discovery to clinical applications[J]. Adv Immunol, 2004, 82 : 249-93. [14] Vlad AM, Kettel JC, Alajez NM, et al. MUC1 immunobiology: from discovery to clinical applications[J]. Adv Immunol, 2004, 82: 249-93. doi: 10.1016/S0065-2776(04)82006-6
[15] Ramlau R, Quoix E, Rolski J, et al. A phase Ⅱ study of TG4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage Ⅲ/Ⅳ non-small-cell lung cancer[J]. J Thorac Oncol, 20 08, 3(7): 735-44. [15] Ramlau R, Quoix E, Rolski J, et al. A phase Ⅱ study of TG4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage Ⅲ/Ⅳ non-small-cell lung cancer[J]. J Thorac Oncol, 2008, 3(7): 735-44. doi: 10.1097/JTO.0b013e31817c6b4f
[16] Agrawal B, Krantz MJ, Reddish MA, et al. Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2[J]. Nat Med, 1998, 4(1): 43-9. [16] Agrawal B, Krantz MJ, Reddish MA, et al. Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2[J]. Nat Med, 1998, 4(1): 43-9. doi: 10.1038/nm0198-043
[17] Quoix E, Ramlau R, Westeel V, et al. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial[J]. Lancet Oncol, 2011, 12 (12): 1125-33. [17] Quoix E, Ramlau R, Westeel V, et al. Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial[J]. Lancet Oncol, 2011, 12(12): 1125-33. doi: 10.1016/S1470-2045(11)70259-5
[18] Rodríguez PC, Rodríguez G, González G, et al. Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy[J]. MEDICC Rev, 2010, 12(1): 17-23.
[18] Rodríguez PC, Rodríguez G, González G, et al. Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy[J]. MEDICC Rev, 2010, 12 (1): 17-23. [19] García B, Neninger E, de la Torre A, et al. Effective inhibition of the epidermal growth factor/epidermal growth factor receptor binding by antiepidermal growth factor antibodies is related to better survival in advanced non-small-cell lung cancer patients treated with the epidermal growth factor cancer vaccine[J]. Clin Cancer Res, 2008, 14(3): 840-6. [19] García B, Neninger E, de la Torre A, et al. Effective inhibition of the epidermal growth factor/epidermal growth factor receptor binding by antiepidermal growth factor antibodies is related to better survival in advanced non-small-cell lung cancer patients treated with the epidermal growth factor cancer vaccine[J]. Clin Cancer Res, 2008, 14(3): 840-6. doi: 10.1158/1078-0432.CCR-07-1050
[20] Neninger Vinageras E, de la Torre A, Osorio Rodríguez M, et al. Phase Ⅱ randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer[J]. J Clin Oncol, 2008, 26(9): 1452-8. doi: 10.1200/JCO.2007.11.5980
[20] Neninger Vinageras E, de la Torre A, Osorio Rodríguez M, et al. Phase Ⅱ randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer[J]. J Clin Oncol, 2008, 26(9): 1452-8. [21] Sangha R, Butts C. L-BLP25: a peptide vaccine strategy in non-small-cell lung cancer[J]. Clin Cancer Res, 2007, 13(15Pt 2): 4652s-4.
[21] Sangha R, Butts C. L-BLP25: a peptide vaccine strategy in nonsmall- cell lung cancer[J]. Clin Cancer Res, 2007, 13(15Pt 2): 46 52s-4. [22] Butts C, Murray N, Maksymiuk A, et al. Randomized phase ⅡB trial of BLP25 liposome vaccine in stage ⅢB and Ⅳ non-smallcell lung cancer[J]. J Clin Oncol, 2005, 23(27): 6674-81. [22] Butts C, Murray N, Maksymiuk A, et al. Randomized phase ⅡB trial of BLP25 liposome vaccine in stage ⅢB and Ⅳ non-small-cell lung cancer[J]. J Clin Oncol, 2005, 23(27): 6674-81. doi: 10.1200/JCO.2005.13.011
[23] Butts CA, Socinski MA, Mitchell P, et al. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage Ⅲ non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial[J]. Lancet Oncol, 2014, 15(1): 59-68. doi: 10.1016/S1470-2045(13)70510-2
[23] Butts CA, Socinski MA, Mitchell P, et al. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage Ⅲ non-smallcell lung cancer (START): a randomised, double-blind, phase 3 trial[J]. Lancet Oncol, 2014, 15(1): 59-68. [24] Kakimi K, Isobe M, Uenaka A, et al. A phase Ⅰ study of vaccination with NYESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen[J]. Int J Cancer, 2011, 129(12): 2836-46. [24] Kakimi K, Isobe M, Uenaka A, et al. A phase Ⅰ study of vaccination with NYESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen[J]. Int J Cancer, 2011, 129(12): 2836-46. doi: 10.1002/ijc.25955
[25] Eikawa S, Kakimi K, Isobe M, et al. Induction of CD8 T-cell responses restricted to multiple HLA class Ⅰ alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91 -110) peptide[J]. Int J Cancer, 2013, 132(2): 345-54. [25] Eikawa S, Kakimi K, Isobe M, et al. Induction of CD8 T-cell responses restricted to multiple HLA class Ⅰ alleles in a cancer patient by immunization with a 20-mer NY-ESO-1f (NY-ESO-1 91-110) peptide[J]. Int J Cancer, 2013, 132(2): 345-54. doi: 10.1002/ijc.27682
[26] Wada H, Isobe M, Kakimi K, et al. Vaccination with NY-ESO-1 overlapping peptides mixed with picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen[J]. J Immunother, 2014, 37(2): 84-92. doi: 10.1097/CJI.0000000000000017
[26] Wada H, Isobe M, Kakimi K, et al. Vaccination with NY-ESO-1 overlapping peptides mixed with picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen[J]. J Immunother, 2014, 37(2): 84-92. [27] Malykh YN, Schauer R, Shaw L. N-Glycolylneuraminic acid in human tumours[J]. Biochimie, 2001, 83(7): 623-34. doi: 10.1016/S0300-9084(01)01303-7
[27] Malykh YN, Schauer R, Shaw L. N-Glycolylneuraminic acid in human tumours[J]. Biochimie, 2001, 83(7): 623-34. [28] Vázquez AM1, Hernández AM, Macías A, et al. Racotumomab: an anti-idiotype vaccine related to N-glycolyl-containing gangliosides-preclinical and clinical data[J]. Front Oncol, 2012, 2: 150. [28] Vázquez AM1, Hernández AM, Macías A, et al. Racotumomab: an anti-idiotype vaccine related to N-glycolyl-containing gangliosides-preclinical and clinical data[J]. Front Oncol, 2012, 2: 150.
[29] Neninger E, Díaz RM, de la Torre A, et al. Active immunotherapy with IE10 anti-idiotype vaccine in patients with small cell lung cancer: report of a phase Ⅰ trial[J]. Cancer Biol Ther, 2007, 6(2): 145-50. doi: 10.4161/cbt.6.2.3574
[29] Neninger E, Díaz RM, de la Torre A, et al. Active immunotherapy with IE10 anti-idiotype vaccine in patients with small cell lung cancer: report of a phase Ⅰ trial[J]. Cancer Biol Ther, 2007, 6(2): 14 5-50. [30] Alfonso S, Valdés-Zayas A, Santiesteban ER, et al. A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients[J]. Clin Cancer Res, 2014, 20(14): 3660-71. doi: 10.1158/1078-0432.CCR-13-1674
[30] Alfonso S, Valdés-Zayas A, Santiesteban ER, et al. A randomized, multicenter, placebo-controlled clinical trial of racotumomabalum vaccine as switch maintenance therapy in advanced nonsmall cell lung cancer patients[J]. Clin Cancer Res, 2014, 20(14): 36 60-71. [31] Nemunaitis J, Dillman RO, Schwarzenberger PO, et al. Phase Ⅱstudy of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer[J]. J Clin Oncol, 2006, 24(2): 4721-30.
[31] Nemunaitis J, Dillman RO, Schwarzenberger PO, et al. Phase Ⅱ study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in nonsmall- cell lung cancer[J]. J Clin Oncol, 2006, 24(2): 4721-30. [32] Nemunaitis J, Murray N. Immune-modulating vaccines in non-small-cell lung cancer[J]. J Thorac Oncol, 2006, 1(7): 756-61.
[32] Nemunaitis J, Murray N. Immune-modulating vaccines in nonsmall- cell lung cancer[J]. J Thorac Oncol, 2006, 1(7): 756-61. [33] Giaccone G, Bazhenova LA, Nemunaitis J, et al. A phase Ⅲ study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer[J].Eur J Cancer, 2015, 51(16): 2321-9. [33] Giaccone G, Bazhenova LA, Nemunaitis J, et al. A phase Ⅲ study of belagenpumatucel-L, an allogeneic tumour cell vaccine, as maintenance therapy for non-small cell lung cancer[J].Eur J Cancer, 2015, 51(16): 2321-9. doi: 10.1016/j.ejca.2015.07.035
[34] Tuyaerts S, Aerts JL, Corthals J, et al. Current approaches in dendritic cell generation and future implications for cancer immunotherapy[J]. Cancer Immunol Immunother, 2007, 56(10): 1513-37. doi: 10.1007/s00262-007-0334-z
[34] Tuyaerts S, Aerts JL, Corthals J, et al. Current approaches in dendritic cell generation and future implications for cancer immunotherapy[J]. Cancer Immunol Immunother, 2007, 56(10): 15 13-37. [35] Chiappori AA, Soliman H, Janssen WE, et al. INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect [J]. Expert Opin Biol Ther, 20l0, 10 (6): 983-91. [35] Chiappori AA, Soliman H, Janssen WE, et al. INGN-225: a dendritic cell-based p53 vaccine (Ad.p53-DC) in small cell lung cancer: observed association between immune response and enhanced chemotherapy effect [J]. Expert Opin Biol Ther, 20l0, 10(6): 983-91. doi: 10.1517/14712598.2010.484801
[36] Um SJ, Choi YJ, Shin HJ, et al. Phase Ⅰ study of autologous dendritic cell tumor vaccine in patients with non-small cell lung cancer[J]. Lung Cancer, 2010, 70(2): 188-94. [36] Um SJ, Choi YJ, Shin HJ, et al. Phase Ⅰ study of autologous dendritic cell tumor vaccine in patients with non-small cell lung cancer[J]. Lung Cancer, 2010, 70(2): 188-94. doi: 10.1016/j.lungcan.2010.02.006
[37] Nemunaitis J, Sterman D, Jablons D, et al. Granulocytemacrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer[J]. J Natl Cancer Inst, 2004, 96(2): 326-31. [37] Nemunaitis J, Sterman D, Jablons D, et al. Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer[J]. J Natl Cancer Inst, 2004, 96(2): 326-31.
[38] Nemunaitis J, Jahan T, Ross H, et al. Phase 1/2 trial of autologous tumor mixed with an allogeneic GVAX vaccine in advanced-stage non-small-cell lung cancer[J]. Cancer Gene Therapy, 2006, 13(6): 555-62. doi: 10.1038/sj.cgt.7700922
[38] Nemunaitis J, Jahan T, Ross H, et al. Phase 1/2 trial of autologous tumor mixed with an allogeneic GVAX vaccine in advanced-stage non-small-cell lung cancer[J]. Cancer Gene Therapy, 2006, 13(6): 55 5-62. [39] Dessureault S, Alsarraj M, McCarthy S, et al. A GMCSF/CD40L producing cell augments anti-tumor T cell responses[J]. J Surg Res, 2005, 125(2): 173-81. [39] Dessureault S, Alsarraj M, McCarthy S, et al. A GMCSF/CD40L producing cell augments anti-tumor T cell responses[J]. J Surg Res, 2005, 125(2): 173-81. doi: 10.1016/j.jss.2004.11.036
[40] Creelan BC, Antonia S, Noyes D, et al. Phase Ⅱ trial of a GM-CSF-producing and CD40L-expressing bystander cell line combined with an allogeneic tumor cell-based vaccine for refractory lung adenocarcinoma[J]. J Immunother, 2013, 36(8): 442-50. doi: 10.1097/CJI.0b013e3182a80237
[40] Creelan BC, Antonia S, Noyes D, et al. Phase Ⅱ trial of a GMCSF- producing and CD40L-expressing bystander cell line combined with an allogeneic tumor cell-based vaccine for refractory lung adenocarcinoma[J]. J Immunother, 2013, 36(8): 44 2-50. [41] Sharma S, Yang SC, Hillinger S, et al. CCL21-mediated anti-tumor responses require IFN gamma, MIG/CXCL9 and IP-10/CXCL10[J]. Mol Cancer, 2003, 2: 22. doi: 10.1186/1476-4598-2-22
[41] Sharma S, Yang SC, Hillinger S, et al. CCL21-mediated antitumor responses require IFN gamma, MIG/CXCL9 and IP-10/ CXCL10[J]. Mol Cancer, 2003, 2: 22. [42] Takano A, Nakamura Y, Daigo Y. Characterization of a lung cancer growth factor, LASEP3 as a serological and prognostic biomarker and therapeutic target[J]. Ann Oncol, 2013, 24(suppl 9): ix31-65. [42] Takano A, Nakamura Y, Daigo Y. Characterization of a lung cancer growth factor, LASEP3 as a serological and prognostic biomarker and therapeutic target[J]. Ann Oncol, 2013, 24(suppl 9): ix31-65.
[43] Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma[J]. N Engl J Med, 2012, 366(10): 925-31. doi: 10.1056/NEJMoa1112824
[43] Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a patient with melanoma[J]. N Engl J Med, 2012, 366(10): 925-31. [44] Hiniker SM, Chen DS, Reddy S, et al. A systemic complete response of metastatic melanoma to local radiation and immunotherapy[J]. Transl Oncol, 2012, 5(6): 404-7. doi: 10.1593/tlo.12280
[44] Hiniker SM, Chen DS, Reddy S, et al. A systemic complete response of metastatic melanoma to local radiation and immunotherapy[J]. Transl Oncol, 2012, 5(6): 404-7. [45] Golden EB, Demaria S, Schiff PB, et al. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer[J]. Cancer Immunol Res, 2013, 1(6): 365-72. [45] Golden EB, Demaria S, Schiff PB, et al. An abscopal response to radiation and ipilimumab in a patient with metastatic non-small cell lung cancer[J]. Cancer Immunol Res, 2013, 1(6): 365-72. doi: 10.1158/2326-6066.CIR-13-0115
[46] Harper J, Sainson RC. Regulation of the anti-tumor immune response by cancer-associated fibroblasts[J]. Semin Cancer Biol, 20 14, 25: 69-77. [46] Harper J, Sainson RC. Regulation of the anti-tumor immune response by cancer-associated fibroblasts[J]. Semin Cancer Biol, 2014, 25: 69-77. doi: 10.1016/j.semcancer.2013.12.005
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