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集落刺激因子联合放疗对抗肿瘤免疫调节的相关研究进展
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Abstract:
集落刺激因子(Colony-stimulating factor, CSF)是一种细胞因子，可以预防或治疗化学治疗引起的中性粒细胞减少，主要用于接受化疗或接受高度血液毒性治疗方案的患者。随着现代放射治疗技术和支持治疗的发展，放化疗与集落刺激因子的联合治疗值得被重新评估。放射治疗在体内和体外均可诱导免疫系统介导的抗癌全身效应。这种效果在联合CSF的创新放射治疗模式的临床前和临床试验中得到了加强。到目前为止，放疗与CSF的联合效应尚未与免疫疗法相结合。然而，它可能在引发针对癌细胞的免疫应答中起主要作用，进而诱导远隔效应。本文通过对集落刺激因子、放疗和免疫治疗联合疗法的有效性,以及放疗联合集落刺激因子对抗肿瘤免疫调节方面的最新研究进行综述，进一步评估集落刺激因子与放疗及免疫治疗联用的可行性。
Colony-stimulating factor (CSF) is a cytokine that can prevent or treat chemotherapy-induced neu-tropenia, primarily in patients receiving chemotherapy or receiving highly hematotoxic treatment regimens. With the development of modern radiotherapy techniques and supportive care, the com-bination of chemoradiotherapy and colony-stimulating factor deserves to be re-evaluated. Radiation therapy can induce systemic effects mediated by the immune system against cancer both in vivo and in vitro. This effect is reinforced in preclinical and clinical trials of an innovative radiotherapy modality in combination with CSF. So far, the combined effect of radiotherapy with CSF has not been combined with immunotherapy. However, it may play a major role in eliciting an immune response against cancer cells, which in turn induces the distancing effect. This article reviews the effective-ness of the combination of colony-stimulating factor, radiotherapy and immunotherapy, as well as the latest research on the immunomodulation of radiotherapy combined with colony-stimulating factor against tumors, and further evaluates the feasibility of combining colony-stimulating factors with radiotherapy and immunotherapy.
| [1] | Crawford, J., Dale, D.C. and Lyman, G.H. (2004) Chemotherapy-Induced Neutropenia: Risks, Consequences, and New Directions for Its Management. Cancer, 100, 228-237. https://doi.org/10.1002/cncr.11882 |
| [2] | Ouyang, Z., Peng, D. and Dhakal, D.P. (2013) Risk Factors for Hematological Toxicity of Chemotherapy for Bone and Soft Tissue Sar-coma. Oncology Letters, 5, 1736-1740. https://doi.org/10.3892/ol.2013.1234 |
| [3] | Li, M., Li, X., Guo, Y., Miao, Z., Liu, X., Guo, S. and Zhang, H. (2020) Development and Assessment of an Individualized Nomogram to Predict Colo-rectal Cancer Liver Metastases. Quantitative Imaging in Medicine and Surgery, 10, 397-414. https://doi.org/10.21037/qims.2019.12.16 |
| [4] | Stern, A.C. and Jones, T.C. (1992) The Side-Effect Profile of GM-CSF. Infection, 20, S124-S127.
https://doi.org/10.1007/BF01705031 |
| [5] | Ushach, I. and Zlotnik, A. (2016) Biological Role of Granulocyte Mac-rophage Colony-Stimulating Factor (GM-CSF) and Macrophage Colony-Stimulating Factor (M-CSF) on Cells of the Myeloid Lineage. Journal of Leukocyte Biology, 100, 481-489. https://doi.org/10.1189/jlb.3RU0316-144R |
| [6] | Mehta, H.M., Malandra, M. and Corey, S.J. (2015) G-CSF and GM-CSF in Neutropenia. Journal of Immunology, 195, 1341-1349. https://doi.org/10.4049/jimmunol.1500861 |
| [7] | Stinchcombe, T.E. and Gore, E.M. (2010) Limited-Stage Small Cell Lung Cancer: Current Chemoradiotherapy Treatment Paradigms. The Oncologist, 15, 187-195. https://doi.org/10.1634/theoncologist.2009-0298 |
| [8] | Aupérin, A., Le Péchoux, C., Rolland, E., Curran, W.J., Fu-ruse, K., Fournel, P., Belderbos, J., Clamon, G., Ulutin, H.C., Paulus, R., et al. (2010) Meta-Analysis of Concomitant versus Sequential Radiochemotherapy in Locally Advanced Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 28, 2181-2190.
https://doi.org/10.1200/JCO.2009.26.2543 |
| [9] | Joshi, S.S. and Badgwell, B.D. (2021) Current Treatment and Re-cent Progress in Gastric Cancer. CA: A Cancer Journal for Clinicians, 71, 264-279. https://doi.org/10.3322/caac.21657 |
| [10] | Schrag, D., Shi, Q., Weiser, M.R., Gollub, M.J., Saltz, L.B., Musher, B.L., Goldberg, J., Al Baghdadi, T., Goodman, K.A., McWilliams, R.R., et al. (2023) Preoperative Treatment of Locally Ad-vanced Rectal Cancer. The New England Journal of Medicine, 389, 322-334. https://doi.org/10.1056/NEJMoa2303269 |
| [11] | Versteijne, E., van Dam, J.L., Suker, M., Janssen, Q.P., Groothuis, K., Akkermans-Vogelaar, J.M., Besselink, M.G., Bonsing, B.A., Buijsen, J., Busch, O.R., et al. (2022) Neoadjuvant Chemoradiotherapy versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. Journal of Clinical Oncology, 40, 1220-1230. https://doi.org/10.1200/JCO.21.02233 |
| [12] | Tang, L.L., Guo, R., Zhang, N., Deng, B., Chen, L., Cheng, Z.B., Huang, J., Hu, W.H., Huang, S.H., Luo, W.J., et al. (2022) Effect of Radiotherapy Alone vs Radiotherapy with Concur-rent Chemoradiotherapy on Survival without Disease Relapse in Patients with Low-Risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial. JAMA, 328, 728-736. https://doi.org/10.1001/jama.2022.13997 |
| [13] | Klastersky, J., de Naurois, J., Rolston, K., Rapoport, B., Maschmeyer, G., Aapro, M. and Herrstedt, J. (2016) Management of Febrile Neutropaenia: ESMO Clinical Practice Guidelines. Annals of Oncology, 27, v111-v118.
https://doi.org/10.1093/annonc/mdw325 |
| [14] | Asna, N., Livoff, A., Batash, R., Debbi, R., Schaffer, P., Rivkind, T. and Schaffer, M. (2018) Radiation Therapy and Immunotherapy—A Potential Combination in Cancer Treatment. Current Oncology, 25, 454-460.
https://doi.org/10.3747/co.25.4002 |
| [15] | Takeshima, T., Pop, L.M., Laine, A., Iyengar, P., Vitetta, E.S. and Hannan, R. (2016) Key Role for Neutrophils in Radiation-Induced Antitumor Immune Responses: Potentiation with G-CSF. Pro-ceedings of the National Academy of Sciences of the United States of America, 113, 11300-11305. https://doi.org/10.1073/pnas.1613187113 |
| [16] | Liu, Y., Dong, Y., Kong, L., Shi, F., Zhu, H. and Yu, J. (2018) Abscopal Effect of Radiotherapy Combined with Immune Checkpoint Inhibitors. Journal of Hematology & Oncology, 11, Article No. 104.
https://doi.org/10.1186/s13045-018-0647-8 |
| [17] | Leary, R., Gardner, R.B., Mockbee, C. and Roychowdhury, D.F. (2019) Boosting Abscopal Response to Radiotherapy with Sargramostim: A Review of Data and Ongoing Studies. Cu-reus, 11, e4276. https://doi.org/10.7759/cureus.4276 |
| [18] | Aliru, M.L., Schoenhals, J.E., Venkatesulu, B.P., An-derson, C.C., Barsoumian, H.B., Younes, A.I., Ls, K.M., Soeung, M., Aziz, K.E., Welsh, J.W., et al. (2018) Radiation Therapy and Immunotherapy: What Is the Optimal Timing or Sequencing? Immunotherapy, 10, 299-316. https://doi.org/10.2217/imt-2017-0082 |
| [19] | Mouchemore, K.A. and Anderson, R.L. (2021) Immunomodulatory Effects of G-CSF in Cancer: Therapeutic Implications. Seminars in Immunology, 54, Article ID: 101512. https://doi.org/10.1016/j.smim.2021.101512 |
| [20] | Kumar, A., Taghi Khani, A., Sanchez Ortiz, A. and Swaminathan, S. (2022) GM-CSF: A Double-Edged Sword in Cancer Immunotherapy. Frontiers in Immunology, 13, Article 901277. https://doi.org/10.3389/fimmu.2022.901277 |
| [21] | Bhattacharya, P., Budnick, I., Singh, M., Thiruppathi, M., Alhar-shawi, K., Elshabrawy, H., Holterman, M.J. and Prabhakar, B.S. (2015) Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy. Journal of Interferon & Cytokine Research, 35, 585-599. https://doi.org/10.1089/jir.2014.0149 |
| [22] | van de Laar, L., Coffer, P.J. and Woltman, A.M. (2012) Regulation of Dendritic Cell Development by GM-CSF: Molecular Control and Implications for Immune Homeostasis and Therapy. Blood, 119, 3383-3393.
https://doi.org/10.1182/blood-2011-11-370130 |
| [23] | Bhattacharya, P., Thiruppathi, M., Elshabrawy, H.A., Alhar-shawi, K., Kumar, P. and Prabhakar, B.S. (2015) GM-CSF: An Immune Modulatory Cytokine That Can Suppress Au-toimmunity. Cytokine, 75, 261-271.
https://doi.org/10.1016/j.cyto.2015.05.030 |
| [24] | Xu, S., H？glund, M., Hakansson, L. and Venge, P. (2000) Granu-locyte Colony-Stimulating Factor (G-CSF) Induces the Production of Cytokines in Vivo. British Journal of Haematology, 108, 848-853.
https://doi.org/10.1046/j.1365-2141.2000.01943.x |
| [25] | Mehta, H.M. and Corey, S.J. (2021) G-CSF, the Guardian of Granulopoiesis. Seminars in Immunology, 54, Article ID: 101515. https://doi.org/10.1016/j.smim.2021.101515 |
| [26] | Schaue, D., Comin-Anduix, B., Ribas, A., Zhang, L., Goodglick, L., Sayre, J.W., Debucquoy, A., Haustermans, K. and McBride, W.H. (2008) T-Cell Responses to Survivin in Cancer Patients Undergoing Radiation Therapy. Clinical Cancer Research, 14, 4883-4890. https://doi.org/10.1158/1078-0432.CCR-07-4462 |
| [27] | Kachikwu, E.L., Iwamoto, K.S., Liao, Y.P., DeMarco, J.J., Agazaryan, N., Economou, J.S., McBride, W.H. and Schaue, D. (2011) Radiation Enhances Regulatory T Cell Repre-sentation. International Journal of Radiation Oncology, Biology, Physics, 81, 1128-1135. https://doi.org/10.1016/j.ijrobp.2010.09.034 |
| [28] | Demaria, S., Golden, E.B. and Formenti, S.C. (2015) Role of Local Radiation Therapy in Cancer Immunotherapy. JAMA Oncology, 1, 1325-1332. https://doi.org/10.1001/jamaoncol.2015.2756 |
| [29] | Formenti, S.C. and Demaria, S. (2009) Systemic Effects of Local Radiotherapy. Lancet Oncology, 10, 718-726.
https://doi.org/10.1016/S1470-2045(09)70082-8 |
| [30] | Spiotto, M., Fu, Y.X. and Weichselbaum, R.R. (2016) The Intersection of Radiotherapy and Immunotherapy: Mechanisms and Clinical Implications. Science Immunology, 1, eaag1266. https://doi.org/10.1126/sciimmunol.aag1266 |
| [31] | Barker, H.E., Paget, J.T., Khan, A.A. and Harrington, K.J. (2015) The Tumour Microenvironment after Radiotherapy: Mechanisms of Resistance and Recurrence. Nature Re-views Cancer, 15, 409-425. https://doi.org/10.1038/nrc3958 |
| [32] | Gupta, A., Probst, H.C., Vuong, V., Landsham-mer, A., Muth, S., Yagita, H., Schwendener, R., Pruschy, M., Knuth, A. and van den Broek, M. (2012) Radiotherapy Promotes Tumor-Specific Effector CD8+ T Cells via Dendritic Cell Activation. The Journal of Immunology, 189, 558-566. https://doi.org/10.4049/jimmunol.1200563 |
| [33] | Zhao, H., Guo, M., Sun, X., Sun, W., Hu, H., Wei, L. and Ai, H. (2013) Effects of Recombinant Human Granulocyte Colony-Stimulating Factor on Central and Peripheral T Lymphocyte Reconstitution after Sublethal Irradiation in Mice. Journal of Radiation Research, 54, 83-91. https://doi.org/10.1093/jrr/rrs082 |
| [34] | Cui, Y.H., Suh, Y., Lee, H.J., Yoo, K.C., Uddin, N., Jeong, Y.J., Lee, J.S., Hwang, S.G., Nam, S.Y., Kim, M.J., et al. (2015) Radiation Promotes Invasiveness of Non-Small-Cell Lung Cancer Cells through Granulocyte-Colony-Stimulating Factor. Oncogene, 34, 5372-5382. https://doi.org/10.1038/onc.2014.466 |
| [35] | Kantoff, P.W., Higano, C.S., Shore, N.D., Berger, E.R., Small, E.J., Penson, D.F., Redfern, C.H., Ferrari, A.C., Dreicer, R., Sims, R.B., et al. (2010) Sipuleucel-T Immunotherapy for Cas-tration-Resistant Prostate Cancer. The New England Journal of Medicine, 363, 411-422. https://doi.org/10.1056/NEJMoa1001294 |
| [36] | Higano, C.S., Schellhammer, P.F., Small, E.J., Burch, P.A., Nemunaitis, J., Yuh, L., Provost, N. and Frohlich, M.W. (2009) Integrated Data from 2 Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trials of Active Cellular Immunotherapy with Sipuleucel-T in Advanced Prostate Cancer. Cancer, 115, 3670-3679.
https://doi.org/10.1002/cncr.24429 |
| [37] | Kohanbash, G., McKaveney, K., Sakaki, M., Ueda, R., Mintz, A.H., Amankulor, N., Fujita, M., Ohlfest, J.R. and Okada, H. (2013) GM-CSF Promotes the Immunosuppressive Activity of Glioma-Infiltrating Myeloid Cells through Interleukin-4 Receptor-α. Cancer Research, 73, 6413-6423. https://doi.org/10.1158/0008-5472.CAN-12-4124 |
| [38] | Chen, L., Imamichi, S., Tong, Y., Sasaki, Y., Onodera, T., Nakamura, S., Igaki, H., Itami, J. and Masutani, M. (2021) A Combination of GM-CSF and Released Factors from Gamma-Irradiated Tumor Cells Enhances the Differentiation of Macrophages from Bone Marrow Cells and Their Anti-gen-Presenting Function and Polarization to Type 1. Medicines, 8, Article 35. https://doi.org/10.3390/medicines8070035 |
| [39] | Shi, F., Wang, X., Teng, F., Kong, L. and Yu, J. (2017) Abscopal Effect of Metastatic Pancreatic Cancer after Local Radiotherapy and Granulocyte-Macrophage Colony-Stimulating Factor Therapy. Cancer Biology & Therapy, 18, 137-141. https://doi.org/10.1080/15384047.2016.1276133 |
| [40] | Yu, T.W., Chueh, H.Y., Tsai, C.C., Lin, C.T. and Qiu, J.T. (2016) Novel GM-CSF-Based Vaccines: One Small Step in GM-CSF Gene Optimization, One Giant Leap for Human Vaccines. Human Vaccines & Immunotherapeutics, 12, 3020-3028. https://doi.org/10.1080/21645515.2016.1221551 |
| [41] | Le, D.T., Wang-Gillam, A., Picozzi, V., Greten, T.F., Cro-cenzi, T., Springett, G., Morse, M., Zeh, H., Cohen, D., Fine, R.L., et al. (2015) Safety and Survival with GVAX Pan-creas Prime and Listeria Monocytogenes-Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer. Journal of Clinical Oncology, 33, 1325-1333.
https://doi.org/10.1200/JCO.2014.57.4244 |
| [42] | Golden, E.B., Chhabra, A., Chachoua, A., Adams, S., Donach, M., Fenton-Kerimian, M., Friedman, K., Ponzo, F., Babb, J.S., Goldberg, J., et al. (2015) Local Radiotherapy and Granulo-cyte-Macrophage Colony-Stimulating Factor to Generate Abscopal Responses in Patients with Metastatic Solid Tumours: A Proof-of-Principle Trial. The Lancet Oncology, 16, 795-803. https://doi.org/10.1016/S1470-2045(15)00054-6 |
| [43] | Liu, M., Cai, X. and Zeng, Y. (2019) EP1.04-28 The Ab-scopal Effects of the Combination of Radiotherapy and GM-CSF for Patients with Metastatic Thoracic Cancers. Journal of Thoracic Oncology, 14, S980.
https://doi.org/10.1016/j.jtho.2019.08.2153 |
| [44] | Jiang, H., Yu, K., Cui, Y., Ren, X., Li, M., Yang, C., Zhao, X., Zhu, Q. and Lin, S. (2021) Combination of Immunotherapy and Radiotherapy for Recurrent Malignant Gliomas: Results from a Prospective Study. Frontiers in Immunology, 12, Article 632547. https://doi.org/10.3389/fimmu.2021.632547 |
| [45] | Kim, H.R., Kim, K.H., Kong, D.S., Seol, H.J., Nam, D.H., Lim, D.H. and Lee, J.I. (2015) Outcome of Salvage Treatment for Recurrent Glioblastoma. Journal of Clinical Neuroscience, 22, 468-473.
https://doi.org/10.1016/j.jocn.2014.09.018 |
| [46] | Muenst, S., L？ubli, H., Soysal, S.D., Zippelius, A., Tzankov, A. and Hoeller, S. (2016) The Immune System and Cancer Evasion Strategies: Therapeutic Concepts. Journal of Internal Medicine, 279, 541-562.
https://doi.org/10.1111/joim.12470 |
| [47] | Weber, J. (2007) Review: Anti-CTLA-4 Antibody Ipilimumab: Case Studies of Clinical Response and Immune-Related Adverse Events. The Oncologist, 12, 864-872. https://doi.org/10.1634/theoncologist.12-7-864 |
| [48] | Herbst, R.S., Soria, J.C., Kowanetz, M., Fine, G.D., Hamid, O., Gordon, M.S., Sosman, J.A., McDermott, D.F., Powderly, J.D., Gettinger, S.N., et al. (2014) Predictive Correlates of Response to the Anti-PD-L1 Antibody MPDL3280A in Cancer Patients. Nature, 515, 563-567. https://doi.org/10.1038/nature14011 |
| [49] | Hodi, F.S., Lee, S., McDermott, D.F., Rao, U.N., Butterfield, L.H., Tarhini, A.A., Leming, P., Puzanov, I., Shin, D. and Kirkwood, J.M. (2014) Ipilimumab plus Sargramostim vs Ipili-mumab Alone for Treatment of Metastatic Melanoma: A Randomized Clinical Trial. JAMA, 312, 1744-1753. https://doi.org/10.1001/jama.2014.13943 |
| [50] | Babiker, H., Brana, I., Mahadevan, D., Owonikoko, T., Calvo, E., Rischin, D., Moreno, V., Papadopoulos, K.P., Crittenden, M., Formenti, S., et al. (2021) Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. The Oncologist, 26, e1508-e1513. https://doi.org/10.1002/onco.13810 |
| [51] | Zhao, X., Kong, Y. and Zhang, L. (2020) Anti-PD-1 Immunotherapy Combined with Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Negative Patient with Refractory Metastatic Esophageal Squamous Cell Carcinoma: A Case Report and Literature Review. Frontiers in Oncol-ogy, 10, Article 1625.
https://doi.org/10.3389/fonc.2020.01625 |
| [52] | Kong, Y., Zhao, X., Xu, M., Pan, J., Ma, Y., Zou, L., Peng, Q., Zhang, J., Su, C., Xu, Z., et al. (2022) PD-1 Inhibitor Combined with Radiotherapy and GM-CSF (PRaG) in Patients with Metastatic Solid Tumors: An Open-Label Phase II Study. Frontiers in Immunology, 13, Article 952066. https://doi.org/10.3389/fimmu.2022.952066 |
| [53] | He, H., Xu, T., Li, P., Jia, G., Li, X. and Song, Q. (2021) An-ti-PD-1 Immunotherapy Combined with Stereotactic Body Radiation Therapy and GM-CSF as Salvage Therapy in a PD-L1-Positive Patient with Refractory Metastatic Thyroid Hürthle Cell Carcinoma: A Case Report and Literature Re-view. Frontiers in Oncology, 11, Article 782646.
https://doi.org/10.3389/fonc.2021.782646 |
| [54] | Wang, Y., Li, W., Zuo, X., Min, K., Tang, Y., Chen, H., Wang, W. and Zhou, Y. (2023) Anti-PD-1 Immunotherapy Combined with Stereotactic Body Radiation Therapy and GM-CSF for the Treatment of Advanced Malignant PEComa: A Case Report. Frontiers in Oncology, 13, Article 1045119. https://doi.org/10.3389/fonc.2023.1045119 |
| [55] | Yang, J., Xing, P., Kong, Y., Xu, M. and Zhang, L. (2023) PD-1 Inhibitor Combined with Radiotherapy and GM-CSF in MSS/pMMR Metastatic Colon Cancer: A Case Report. Fron-tiers in Oncology, 13, Article 1078915.
https://doi.org/10.3389/fonc.2023.1078915 |
| [56] | Ni, J., Zhou, Y., Wu, L., Ai, X., Dong, X., Chu, Q., Han, C., Wang, X. and Zhu, Z. (2021) Sintilimab, Stereotactic Body Radiotherapy and Granulocyte—Macrophage Colony Stimu-lating Factor as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer: Safety Run-In Results of a Multicenter, Single-Arm, Phase II Trial. Radiation Oncology, 16, Article No. 177. https://doi.org/10.1186/s13014-021-01905-3 |
