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肺癌是中国发病率和死亡率最高的恶性肿瘤。既往手术、放疗、化疗等是非小细胞肺癌治疗的主要手段，目前针对肿瘤免疫逃逸的免疫检查点抑制剂等免疫治疗和靶向治疗在其治疗中也发挥了极其重要的作用。然而部分患者对治疗并不敏感，因此寻找预测疗效的生物标志物，对实现肺癌的精准治疗尤为重要。作为肿瘤微环境中免疫细胞的重要补充，外周血淋巴细胞是人体系统免疫的重要组成部分。本文通过系统回顾外周血淋巴细胞在肺癌发生发展、治疗过程中及治疗后的变化，以期为进一步理解非小细胞肺癌进展并制定治疗策略提供新思路。
","endNoteUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=EndNote&id=714","reference":"| 1 | 郑荣寿， 陈茹， 韩冰峰， 等. 2022年中国恶性肿瘤流行情况分析［J］. 中华肿瘤杂志， 2024， 46（3）： 221. |
| 2 | Mithoowani H， Febbraro M. Non-small-cell lung cancer in 2022： a review for general practitioners in oncology［J］. Curr Oncol， 2022， 29（3）： 1828. |
| 3 | Lambrechts D， Wauters E， Boeckx B， et al. Phenotype molding of stromal cells in the lung tumor microenvironment［J］. Nat Med， 2018， 24（8）： 1277. |
| 4 | Hiam-Galvez KJ， Allen BM， Spitzer MH. Systemic immunity in cancer［J］. Nat Rev Cancer， 2021， 21（6）： 345. |
| 5 | Gonzalez H， Hagerling C， Werb Z. Roles of the immune system in cancer： from tumor initiation to metastatic progression［J］. Genes Dev， 2018， 32（19/20）： 1267. |
| 6 | Teng MWL， Galon J， Fridman WH， et al. From mice to humans： developments in cancer immunoediting［J］. J Clin Invest， 2015， 125（9）： 3338. |
| 7 | Dieu-Nosjean MC， Antoine M， Danel C， et al. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures［J］. J Clin Oncol， 2008， 26（27）： 4410. |
| 8 | Mantovani A， Marchesi F， Malesci A， et al. Tumour-associated macrophages as treatment targets in oncology［J］. Nat Rev Clin Oncol， 2017， 14（7）： 399. |
| 9 | Mellman I， Coukos G， Dranoff G. Cancer immunotherapy comes of age［J］. Nature， 2011， 480（7378）： 480. |
| 10 | Wang YY， Zhou N， Liu HS， et al. Circulating activated lymphocyte subsets as potential blood biomarkers of cancer progression［J］. Cancer Med， 2020， 9（14）： 5086. |
| 11 | Liu YY， Yang QF， Yang JS， et al. Characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire in patients with advanced lung cancer［J］. Int J Cancer， 2019， 145（5）： 1423. |
| 12 | Meyer MA， Baer JM， Knolhoff BL， et al. Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance［J］. Nat Commun， 2018， 9（1）： 1250. |
| 13 | Long JH， Hu ZQ， Xue H， et al. Vascular endothelial growth factor （VEGF） impairs the motility and immune function of human mature dendritic cells through the VEGF receptor 2-RhoA-cofilin1 pathway［J］. Cancer Sci， 2019， 110（8）： 2357. |
| 14 | Binnewies M， Mujal AM， Pollack JL， et al. Unleashing type-2 dendritic cells to drive protective antitumor CD4+ T cell immunity［J］. Cell， 2019， 177（3）： 556. |
| 15 | Engelhard V， Conejo-Garcia JR， Ahmed R， et al. B cells and cancer［J］. Cancer Cell， 2021， 39（10）： 1293. |
| 16 | Zhou JB， Min ZH， Zhang D， et al. Enhanced frequency and potential mechanism of B regulatory cells in patients with lung cancer［J］. J Transl Med， 2014， 12： 304. |
| 17 | Wang Y， Schafer CC， Hough KP， et al. Myeloid-derived suppressor cells impair B cell responses in lung cancer through IL-7 and STAT5［J］. J Immunol， 2018， 201（1）： 278. |
| 18 | Russell é， Conroy MJ， Barr MP. Harnessing natural killer cells in non-small cell lung cancer［J］. Cells， 2022， 11（4）： 605. |
| 19 | Shimasaki N， Jain A， Campana D. NK cells for cancer immunotherapy［J］. Nat Rev Drug Discov， 2020， 19（3）： 200. |
| 20 | 何锋， 王小英， 刘宁， 等. 胸腔镜肺癌根治术对非小细胞肺癌患者外周血T淋巴细胞亚群的影响及临床意义［J］. 中国免疫学杂志， 2022， 38（6）： 725. |
| 21 | Ananth AA， Tai LH， Lansdell C， et al. Surgical stress abrogates pre-existing protective T cell mediated anti-tumor immunity leading to postoperative cancer recurrence［J］. PLoS One， 2016， 11（5）： e0155947. |
| 22 | Bosiljcic M， Cederberg RA， Hamilton MJ， et al. Targeting myeloid-derived suppressor cells in combination with primary mammary tumor resection reduces metastatic growth in the lungs［J］. Breast Cancer Res， 2019， 21（1）： 103. |
| 23 | Deng HS， Zhou J， Chen HL， et al. Impact of lymphadenectomy extent on immunotherapy efficacy in postresectional recurred non-small cell lung cancer： a multi-institutional retrospective cohort study［J］. Int J Surg， 2024， 110（1）： 238. |
| 24 | Mathios D， Kim JE， Mangraviti A， et al. Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM［J］. Sci Transl Med， 2016， 8（370）： 370ra180. |
| 25 | Xia Y， Li WT， Li YM， et al. The clinical value of the changes of peripheral lymphocyte subsets absolute counts in patients with non-small cell lung cancer［J］. Transl Oncol， 2020， 13（12）： 100849. |
| 26 | Cho Y， Park S， Byun HK， et al. Impact of treatment-related lymphopenia on immunotherapy for advanced non-small cell lung cancer［J］. Int J Radiat Oncol Biol Phys， 2019， 105（5）： 1065. |
| 27 | Arina A， Gutiontov SI， Weichselbaum RR. Radiotherapy and immunotherapy for cancer： from \"Systemic\" to \"Multisite\"［J］. Clin Cancer Res， 2020， 26（12）： 2777. |
| 28 | Ellsworth SG. Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors［J］. Adv Radiat Oncol， 2018， 3（4）： 512. |
| 29 | Shiraishi Y， Fang P， Xu C， et al. Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer： a propensity matched analysis of the relative risk of proton versus photon-based radiation therapy［J］. Radiother Oncol， 2018， 128（1）： 154. |
| 30 | Xie XX， Lin SH， Welsh JW， et al. Radiation-induced lymphopenia during chemoradiation therapy for non-small cell lung cancer is linked with age， lung V5， and XRCC1 rs25487 genotypes in lymphocytes［J］. Radiother Oncol， 2021， 154： 187. |
| 31 | Brown JM， Carlson DJ， Brenner DJ. The tumor radiobiology of SRS and SBRT： are more than the 5 Rs involved？［J］. Int J Radiat Oncol Biol Phys， 2014， 88（2）： 254. |
| 32 | 徐文才， 郭雷鸣， 崔莹莹， 等. 肺部立体定向放疗对外周血淋巴细胞的影响［J］. 中国癌症杂志， 2020， 30（12）： 1013. |
| 33 | Pike LRG， Bang A， Mahal BA， et al. The impact of radiation therapy on lymphocyte count and survival in metastatic cancer patients receiving PD-1 immune checkpoint inhibitors［J］. Int J Radiat Oncol Biol Phys， 2019， 103（1）： 142. |
| 34 | Zhao QQ， Chen G， Ye LX， et al. Treatment-duration is related to changes in peripheral lymphocyte counts during definitive radiotherapy for unresectable stage III NSCLC［J］. Radiat Oncol， 2019， 14（1）： 86. |
| 35 | Kim N， Myoung Noh J， Lee W， et al. Proton beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer： a comparative analysis of proton versus photon therapy［J］. Radiother Oncol， 2021， 156： 166. |
| 36 | Damen PJJ， Kroese TE， van Hillegersberg R， et al. The influence of severe radiation-induced lymphopenia on overall survival in solid tumors： a systematic review and meta-analysis［J］. Int J Radiat Oncol Biol Phys， 2021， 111（4）： 936. |
| 37 | Jing W， Xu T， Wu LR， et al. Severe Radiation-Induced lymphopenia attenuates the benefit of durvalumab after concurrent chemoradiotherapy for NSCLC［J］. JTO Clin Res Rep， 2022， 3（9）： 100391. |
| 38 | Spigel DR， Faivre-Finn C， Gray JE， et al. Five-year survival outcomes from the PACIFIC trial： durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer［J］. J Clin Oncol， 2022， 40（12）： 1301. |
| 39 | Liu C， Hu QY， Hu K， et al. Increased CD8+CD28+ T cells independently predict better early response to stereotactic ablative radiotherapy in patients with lung metastases from non-small cell lung cancer［J］. J Transl Med， 2019， 17（1）： 120. |
| 40 | Wu LR， Zhu J， Rudqvist NP， et al. T-Cell receptor profiling and prognosis after stereotactic body radiation therapy for stage I non-small-cell lung cancer［J］. Front Immunol， 2021， 12： 719285. |
| 41 | Kim H， Park S， Han KY， et al. Clonal expansion of resident memory T cells in peripheral blood of patients with non-small cell lung cancer during immune checkpoint inhibitor treatment［J］. J Immunother Cancer， 2023， 11（2）： e005509. |
| 42 | Kim CG， Hong MH， Kim KH， et al. Dynamic changes in circulating PD-1+CD8+ T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer［J］. Eur J Cancer， 2021， 143： 113. |
| 43 | Huang AC， Postow MA， Orlowski RJ， et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response［J］. Nature， 2017， 545（7652）： 60. |
| 44 | Flippot R， Teixeira M， Rey-Cardenas M， et al. B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors［J］. J Immunother Cancer， 2024， 12（4）： e008636. |
| 45 | Mazzaschi G， Facchinetti F， Missale G， et al. The circulating pool of functionally competent NK and CD8+ cells predicts the outcome of anti-PD1 treatment in advanced NSCLC［J］. Lung Cancer， 2019， 127： 153. |
| 46 | Xia LL， Guo LM， Kang J， et al. Predictable roles of peripheral IgM memory B cells for the responses to Anti-PD-1 monotherapy against advanced non-small cell lung cancer［J］. Front Immunol， 2021， 12： 759217. |
| 47 | Patel AJ， Willsmore ZN， Khan N， et al. Regulatory B cell repertoire defects predispose lung cancer patients to immune-related toxicity following checkpoint blockade［J］. Nat Commun， 2022， 13（1）： 3148. |
| 48 | Ma WJ， Wei SX， Long SQ， et al. Dynamic evaluation of blood immune cells predictive of response to immune checkpoint inhibitors in NSCLC by multicolor spectrum flow cytometry［J］. Front Immunol， 2023， 14： 1206631. |
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非小细胞肺癌外周血淋巴细胞水平与预后关系的研究进展
岳玉萌, 刘海峰, 张亚男
betway必威登陆网址 (betway.com )学报››2024, Vol. 45››Issue (11): 694-699.
PDF(454 KB)
PDF(454 KB)
非小细胞肺癌外周血淋巴细胞水平与预后关系的研究进展
Progress in the study of changes in peripheral blood lymphocyte levels in non-small cell lung cancer and its relationship with prognosis
肺癌是中国发病率和死亡率最高的恶性肿瘤。既往手术、放疗、化疗等是非小细胞肺癌治疗的主要手段，目前针对肿瘤免疫逃逸的免疫检查点抑制剂等免疫治疗和靶向治疗在其治疗中也发挥了极其重要的作用。然而部分患者对治疗并不敏感，因此寻找预测疗效的生物标志物，对实现肺癌的精准治疗尤为重要。作为肿瘤微环境中免疫细胞的重要补充，外周血淋巴细胞是人体系统免疫的重要组成部分。本文通过系统回顾外周血淋巴细胞在肺癌发生发展、治疗过程中及治疗后的变化，以期为进一步理解非小细胞肺癌进展并制定治疗策略提供新思路。
Lung cancer is the malignant tumor with the highest morbidity and mortality rate in China. Surgery， radiotherapy， and chemotherapy were the primary means of treatment for non-small cell lung cancer in the past.Immunotherapy and targeted therapy， such as immune checkpoint inhibitors against tumor immune escapealso play a vital role in its treatment. However， some patients are not sensitive to the treatment， so finding biomarkers to predict the efficacy of treatment is significant in achieving the precision treatment of lung cancer. Peripheral blood lymphocytes are critical to human systemic immunity as an essential complement of immune cells in the tumor microenvironment. In this paper， we systematically review the changes of peripheral blood lymphocytes in the development of lung cancerduring and after treatmentto further understand the progression of non-small cell lung cancer， thusproviding new ideas for developing therapeutic strategies.
non-small cell lung cancer/peripheral blood lymphocyte subsets
| 1 | 郑荣寿， 陈茹， 韩冰峰， 等. 2022年中国恶性肿瘤流行情况分析［J］.中华肿瘤杂志，2024，46（3）： 221. |
| 2 | Mithoowani H， Febbraro M. Non-small-cell lung cancer in 2022： a review for general practitioners in oncology［J］.Curr Oncol，2022，29（3）： 1828. |
| 3 | Lambrechts D， Wauters E， Boeckx B， et al. Phenotype molding of stromal cells in the lung tumor microenvironment［J］.Nat Med，2018，24（8）： 1277. |
| 4 | Hiam-Galvez KJ， Allen BM， Spitzer MH. Systemic immunity in cancer［J］.Nat Rev Cancer，2021，21（6）： 345. |
| 5 | Gonzalez H， Hagerling C， Werb Z. Roles of the immune system in cancer： from tumor initiation to metastatic progression［J］.Genes Dev，2018，32（19/20）： 1267. |
| 6 | Teng MWL， Galon J， Fridman WH， et al. From mice to humans： developments in cancer immunoediting［J］.J Clin Invest，2015，125（9）： 3338. |
| 7 | Dieu-Nosjean MC， Antoine M， Danel C， et al. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures［J］.J Clin Oncol，2008，26（27）： 4410. |
| 8 | Mantovani A， Marchesi F， Malesci A， et al. Tumour-associated macrophages as treatment targets in oncology［J］.Nat Rev Clin Oncol，2017，14（7）： 399. |
| 9 | Mellman I， Coukos G， Dranoff G. Cancer immunotherapy comes of age［J］.Nature，2011，480（7378）： 480. |
| 10 | Wang YY， Zhou N， Liu HS， et al. Circulating activated lymphocyte subsets as potential blood biomarkers of cancer progression［J］.Cancer Med，2020，9（14）： 5086. |
| 11 | Liu YY， Yang QF， Yang JS， et al. Characteristics and prognostic significance of profiling the peripheral blood T-cell receptor repertoire in patients with advanced lung cancer［J］.Int J Cancer，2019，145（5）： 1423. |
| 12 | Meyer MA， Baer JM， Knolhoff BL， et al. Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance［J］.Nat Commun，2018，9（1）： 1250. |
| 13 | Long JH， Hu ZQ， Xue H， et al. Vascular endothelial growth factor （VEGF） impairs the motility and immune function of human mature dendritic cells through the VEGF receptor 2-RhoA-cofilin1 pathway［J］.Cancer Sci，2019，110（8）： 2357. |
| 14 | Binnewies M， Mujal AM， Pollack JL， et al. Unleashing type-2 dendritic cells to drive protective antitumor CD4+T cell immunity［J］.Cell，2019，177（3）： 556. |
| 15 | Engelhard V， Conejo-Garcia JR， Ahmed R， et al. B cells and cancer［J］.Cancer Cell，2021，39（10）： 1293. |
| 16 | Zhou JB， Min ZH， Zhang D， et al. Enhanced frequency and potential mechanism of B regulatory cells in patients with lung cancer［J］.J Transl Med，2014，12： 304. |
| 17 | Wang Y， Schafer CC， Hough KP， et al. Myeloid-derived suppressor cells impair B cell responses in lung cancer through IL-7 and STAT5［J］.J Immunol，2018，201（1）： 278. |
| 18 | Russell é， Conroy MJ， Barr MP. Harnessing natural killer cells in non-small cell lung cancer［J］.Cells，2022，11（4）： 605. |
| 19 | Shimasaki N， Jain A， Campana D. NK cells for cancer immunotherapy［J］.Nat Rev Drug Discov，2020，19（3）： 200. |
| 20 | 何锋， 王小英， 刘宁， 等. 胸腔镜肺癌根治术对非小细胞肺癌患者外周血T淋巴细胞亚群的影响及临床意义［J］.中国免疫学杂志，2022，38（6）： 725. |
| 21 | Ananth AA， Tai LH， Lansdell C， et al. Surgical stress abrogates pre-existing protective T cell mediated anti-tumor immunity leading to postoperative cancer recurrence［J］.PLoS One，2016，11（5）： e0155947. |
| 22 | Bosiljcic M， Cederberg RA， Hamilton MJ， et al. Targeting myeloid-derived suppressor cells in combination with primary mammary tumor resection reduces metastatic growth in the lungs［J］.Breast Cancer Res，2019，21（1）： 103. |
| 23 | Deng HS， Zhou J， Chen HL， et al. Impact of lymphadenectomy extent on immunotherapy efficacy in postresectional recurred non-small cell lung cancer： a multi-institutional retrospective cohort study［J］.Int J Surg，2024，110（1）： 238. |
| 24 | Mathios D， Kim JE， Mangraviti A， et al. Anti-PD-1 antitumor immunity is enhanced by local and abrogated by systemic chemotherapy in GBM［J］.Sci Transl Med，2016，8（370）： 370ra180. |
| 25 | Xia Y， Li WT， Li YM， et al. The clinical value of the changes of peripheral lymphocyte subsets absolute counts in patients with non-small cell lung cancer［J］.Transl Oncol，2020，13（12）： 100849. |
| 26 | Cho Y， Park S， Byun HK， et al. Impact of treatment-related lymphopenia on immunotherapy for advanced non-small cell lung cancer［J］.Int J Radiat Oncol Biol Phys，2019，105（5）： 1065. |
| 27 | Arina A， Gutiontov SI， Weichselbaum RR. Radiotherapy and immunotherapy for cancer： from "Systemic" to "Multisite"［J］.Clin Cancer Res，2020，26（12）： 2777. |
| 28 | Ellsworth SG. Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors［J］.Adv Radiat Oncol，2018，3（4）： 512. |
| 29 | Shiraishi Y， Fang P， Xu C， et al. Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer： a propensity matched analysis of the relative risk of proton versus photon-based radiation therapy［J］.Radiother Oncol，2018，128（1）： 154. |
| 30 | Xie XX， Lin SH， Welsh JW， et al. Radiation-induced lymphopenia during chemoradiation therapy for non-small cell lung cancer is linked with age， lung V5， and XRCC1 rs25487 genotypes in lymphocytes［J］.Radiother Oncol，2021，154： 187. |
| 31 | Brown JM， Carlson DJ， Brenner DJ. The tumor radiobiology of SRS and SBRT： are more than the 5 Rs involved？［J］.Int J Radiat Oncol Biol Phys，2014，88（2）： 254. |
| 32 | 徐文才， 郭雷鸣， 崔莹莹， 等. 肺部立体定向放疗对外周血淋巴细胞的影响［J］.中国癌症杂志，2020，30（12）： 1013. |
| 33 | Pike LRG， Bang A， Mahal BA， et al. The impact of radiation therapy on lymphocyte count and survival in metastatic cancer patients receiving PD-1 immune checkpoint inhibitors［J］.Int J Radiat Oncol Biol Phys，2019，103（1）： 142. |
| 34 | Zhao QQ， Chen G， Ye LX， et al. Treatment-duration is related to changes in peripheral lymphocyte counts during definitive radiotherapy for unresectable stage III NSCLC［J］.Radiat Oncol，2019，14（1）： 86. |
| 35 | Kim N， Myoung Noh J， Lee W， et al. Proton beam therapy reduces the risk of severe radiation-induced lymphopenia during chemoradiotherapy for locally advanced non-small cell lung cancer： a comparative analysis of proton versus photon therapy［J］.Radiother Oncol，2021，156： 166. |
| 36 | Damen PJJ， Kroese TE， van Hillegersberg R， et al. The influence of severe radiation-induced lymphopenia on overall survival in solid tumors： a systematic review and meta-analysis［J］.Int J Radiat Oncol Biol Phys，2021，111（4）： 936. |
| 37 | Jing W， Xu T， Wu LR， et al. Severe Radiation-Induced lymphopenia attenuates the benefit of durvalumab after concurrent chemoradiotherapy for NSCLC［J］.JTO Clin Res Rep，2022，3（9）： 100391. |
| 38 | Spigel DR， Faivre-Finn C， Gray JE， et al. Five-year survival outcomes from the PACIFIC trial： durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer［J］.J Clin Oncol，2022，40（12）： 1301. |
| 39 | Liu C， Hu QY， Hu K， et al. Increased CD8+CD28+ T cells independently predict better early response to stereotactic ablative radiotherapy in patients with lung metastases from non-small cell lung cancer［J］.J Transl Med，2019，17（1）： 120. |
| 40 | Wu LR， Zhu J， Rudqvist NP， et al. T-Cell receptor profiling and prognosis after stereotactic body radiation therapy for stage I non-small-cell lung cancer［J］.Front Immunol，2021，12： 719285. |
| 41 | Kim H， Park S， Han KY， et al. Clonal expansion of resident memory T cells in peripheral blood of patients with non-small cell lung cancer during immune checkpoint inhibitor treatment［J］.J Immunother Cancer，2023，11（2）： e005509. |
| 42 | Kim CG， Hong MH， Kim KH， et al. Dynamic changes in circulating PD-1+CD8+T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer［J］.Eur J Cancer，2021，143： 113. |
| 43 | Huang AC， Postow MA， Orlowski RJ， et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response［J］.Nature，2017，545（7652）： 60. |
| 44 | Flippot R， Teixeira M， Rey-Cardenas M， et al. B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors［J］.J Immunother Cancer，2024，12（4）： e008636. |
| 45 | Mazzaschi G， Facchinetti F， Missale G， et al. The circulating pool of functionally competent NK and CD8+cells predicts the outcome of anti-PD1 treatment in advanced NSCLC［J］.Lung Cancer，2019，127： 153. |
| 46 | Xia LL， Guo LM， Kang J， et al. Predictable roles of peripheral IgM memory B cells for the responses to Anti-PD-1 monotherapy against advanced non-small cell lung cancer［J］.Front Immunol，2021，12： 759217. |
| 47 | Patel AJ， Willsmore ZN， Khan N， et al. Regulatory B cell repertoire defects predispose lung cancer patients to immune-related toxicity following checkpoint blockade［J］.Nat Commun，2022，13（1）： 3148. |
| 48 | Ma WJ， Wei SX， Long SQ， et al. Dynamic evaluation of blood immune cells predictive of response to immune checkpoint inhibitors in NSCLC by multicolor spectrum flow cytometry［J］.Front Immunol，2023，14： 1206631. |
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