Frontier and hotspot of biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YUAN Lei , SHEN Zhiming , SUN Fei , SHAN Yibo , LU Yi , ZHU Jianwei ,  SHI Hongcan

1. Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Institute of Translational Medicine, Medical College of Yangzhou University, Clinical Medical College of Yangzhou University, Yangzhou, 225009, Jiangsu, P. R. China;

Corresponding author：

SHI Hongcan, Email: shihongcan@yzu.edu.cn

Keywords：

Non-small cell lung cancer; immunotherapy; biomarkers; CiteSpace; visualization analysis

DOI：

10.7507/1007-4848.202208033

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To analyze the current development of researches on biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer and to provide reference for subsequent studies. Methods Studies on biomarkers for predicting the efficacy of immunotherapy for non-small cell lung cancer indexed in the Web of Science Core Collection from 2017 to 2021 were searched by computer. The annual distribution, journals, authors, countries, institutions, and keywords of studies were visualized and analyzed by CiteSpace. Results A total of 426 studies were collected, including 298 articles and 128 reviews. The average number of published studies was about 85, and increased year by year. PD-L1 expression, tumor mutational burden, tumor microenvironment and liquid biopsy were hot keywords in this field. Conclusion In the future, combination of biomarkers in the liquid biopsy and tumor microenvironment with radiomics analysis will be the research hotspot and frontier in this field for more accurate assessment with tumor-related signatures such as lymphocytic immune status and characteristics of tumor lesions in non-small cell lung cancer patients.

Citation： YUAN Lei, SHEN Zhiming, SUN Fei, SHAN Yibo, LU Yi, ZHU Jianwei, SHI Hongcan. Frontier and hotspot of biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2024, 31(4): 562-569. doi: 10.7507/1007-4848.202208033 Copy

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin, 2021, 71(1): 7-33.
3.	Brozos-Vázquez EM, Díaz-Peña R, García-González J, et al. Immunotherapy in nonsmall-cell lung cancer: Current status and future prospects for liquid biopsy. Cancer Immunol Immunother, 2021, 70(5): 1177-1188.
4.	周彩存, 王洁, 王宝成, 等. 中国非小细胞肺癌免疫检查点抑制剂治疗专家共识(2020年版). 中国肺癌杂志, 2021, 24(4): 217-235.
5.	王亚东, 杨笑盈, 贾梓淇, 等. 循环肿瘤细胞PD-L1表达在非小细胞肺癌免疫治疗中的应用. 中国胸心血管外科临床杂志, 2021, 28(1): 110-115.
6.	Liberini V, Mariniello A, Righi L, et al. NSCLC biomarkers to predict response to immunotherapy with checkpoint inhibitors (ICI): From the cells to in vivo images. Cancers (Basel), 2021, 13(18): 4543.
7.	Chen C. A glimpse of the first eight months of the COVID-19 literature on microsoft academic graph: Themes, citation contexts, and uncertainties. Front Res Metr Anal, 2020, 5: 607286.
8.	张雨, 徐燕, 崔倩, 等. 基于Web of Science的国外免疫检查点抑制剂在肺癌治疗中应用的研究现状及热点分析. 现代肿瘤医学, 2022, 30(5): 891-895.
9.	Goodman AM, Kato S, Bazhenova L, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther, 2017, 16(11): 2598-2608.
10.	Kamphorst AO, Pillai RN, Yang S, et al. Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted therapy in lung cancer patients. Proc Natl Acad Sci U S A, 2017, 114(19): 4993-4998.
11.	Bagley SJ, Kothari S, Aggarwal C, et al. Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung Cancer, 2017, 106: 1-7.
12.	Trebeschi S, Drago SG, Birkbak NJ, et al. Predicting response to cancer immunotherapy using noninvasive radiomic biomarkers. Ann Oncol, 2019, 30(6): 998-1004.
13.	Sun J, Zhang Z, Bao S, et al. Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer. J Immunother Cancer, 2020, 8(1): e000110.
14.	Del Re M, Marconcini R, Pasquini G, et al. PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC. Br J Cancer, 2018, 118(6): 820-824.
15.	Aguiar PN, De Mello RA, Hall P, et al. PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: Updated survival data. Immunotherapy, 2017, 9(6): 499-506.
16.	Prelaj A, Tay R, Ferrara R, et al. Predictive biomarkers of response for immune checkpoint inhibitors in non-small-cell lung cancer. Eur J Cancer, 2019, 106: 144-159.
17.	Xia L, Liu Y, Wang Y. PD-1/PD-L1 blockade therapy in advanced non-small-cell lung cancer: Current status and future directions. Oncologist, 2019, 24(Suppl 1): S31-S41.
18.	Malhotra J, Jabbour SK, Aisner J. Current state of immunotherapy for non-small cell lung cancer. Transl Lung Cancer Res, 2017, 6(2): 196-211.
19.	Hanna NH, Robinson AG, Temin S, et al. Therapy for stage Ⅳ non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol, 2021, 39(9): 1040-1091.
20.	Yu Y, Zeng D, Ou Q, et al. Association of survival and immune-related biomarkers with immunotherapy in patients with non-small cell lung cancer: A meta-analysis and individual patient-level analysis. JAMA Netw Open, 2019, 2(7): e196879.
21.	Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer, 2019, 19(3): 133-150.
22.	Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med, 2018, 378(22): 2093-2104.
23.	Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol, 2020, 21(10): 1353-1365.
24.	Litchfield K, Reading JL, Puttick C, et al. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell, 2021, 184(3): 596-614.
25.	方涛, 雷想, 宋兵. 阿特珠单抗在肺癌治疗中的研究进展. 中国胸心血管外科临床杂志, 2022, 29(1): 114-120.
26.	Lei X, Lei Y, Li JK, et al. Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy. Cancer Lett, 2020, 470: 126-133.
27.	Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 2014, 515(7528): 563-567.
28.	Sliker BH, Campbell PM. Fibroblasts influence the efficacy, resistance, and future use of vaccines and immunotherapy in cancer treatment. Vaccines (Basel), 2021, 9(6): 634.
29.	Barrett RL, Puré E. Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy. Elife, 2020, 9: e57243.
30.	Guibert N, Delaunay M, Lusque A, et al. PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab. Lung Cancer, 2018, 120: 108-112.
31.	Boffa DJ, Graf RP, Salazar MC, et al. Cellular expression of PD-L1 in the peripheral blood of lung cancer patients is associated with worse survival. Cancer Epidemiol Biomarkers Prev, 2017, 26(7): 1139-1145.
32.	Ilié M, Szafer-Glusman E, Hofman V, et al. Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer. Ann Oncol, 2018, 29(1): 193-199.
33.	Cabel L, Riva F, Servois V, et al. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: A proof-of-concept study. Ann Oncol, 2017, 28(8): 1996-2001.
34.	Giroux Leprieur E, Herbretau G, Dumenil C, et al. Circulating tumor DNA evaluated by next-generation sequencing is predictive of tumor response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer. Oncoimmunology, 2018, 7(5): e1424675.
35.	Goldberg SB, Narayan A, Kole AJ, et al. Early assessment of lung cancer immunotherapy response via circulating tumor DNA. Clin Cancer Res, 2018, 24(8): 1872-1880.
36.	Alama A, Coco S, Genova C, et al. Prognostic relevance of circulating tumor cells and circulating cell-free DNA association in metastatic non-small cell lung cancer treated with nivolumab. J Clin Med, 2019, 8(7): 1011.
37.	Pasini L, Ulivi P. Liquid biopsy for the detection of resistance mechanisms in NSCLC: Comparison of different blood biomarkers. J Clin Med, 2019, 8(7): 998.
38.	Jiang T, Bai Y, Zhou F, et al. Clinical value of neutrophil-to-lymphocyte ratio in patients with non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors. Lung Cancer, 2019, 130: 76-83.
39.	Möller M, Turzer S, Schütte W, et al. Blood immune cell biomarkers in patient with lung cancer undergoing treatment with checkpoint blockade. J Immunother, 2020, 43(2): 57-66.
40.	Pasini L, Ulivi P. Extracellular vesicles in non-small-cell lung cancer: Functional role and involvement in resistance to targeted treatment and immunotherapy. Cancers (Basel), 2019, 12(1): 40.
41.	Wu J, Li S, Zhang P. Tumor-derived exosomes: Immune properties and clinical application in lung cancer. Cancer Drug Resist, 2022, 5(1): 102-113.
42.	Li C, Li C, Zhi C, et al. Clinical significance of PD-L1 expression in serum-derived exosomes in NSCLC patients. J Transl Med, 2019, 17(1): 355.
43.	Wang JH, Wahid KA, van Dijk LV, et al. Radiomic biomarkers of tumor immune biology and immunotherapy response. Clin Transl Radiat Oncol, 2021, 28: 97-115.
44.	Wang H, Chen YZ, Li WH, et al. Pretreatment thoracic CT radiomic features to predict brain metastases in patients with ALK-rearranged non-small cell lung cancer. Front Genet, 2022, 13: 772090.
45.	徐嘉昕, 钱凯, 蒋立虹. 机器学习算法在肺癌临床诊断及生存预后分析中的应用. 中国胸心血管外科临床杂志, 2022, 29(6): 777-781.
46.	Piñeiro-Fiel M, Moscoso A, Pubul V, et al. A systematic review of PET textural analysis and radiomics in cancer. Diagnostics (Basel), 2021, 11(2): 380.
47.	Jiang M, Sun D, Guo Y, et al. Assessing PD-L1 expression level by radiomic features from PET/CT in nonsmall cell lung cancer patients: An initial result. Acad Radiol, 2020, 27(2): 171-179.
48.	Valentinuzzi D, Vrankar M, Boc N, et al. [18F]FDG PET immunotherapy radiomics signature (iRADIOMICS) predicts response of non-small-cell lung cancer patients treated with pembrolizumab. Radiol Oncol, 2020, 54(3): 285-294.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2021. CA Cancer J Clin, 2021, 71(1): 7-33.
3. Brozos-Vázquez EM, Díaz-Peña R, García-González J, et al. Immunotherapy in nonsmall-cell lung cancer: Current status and future prospects for liquid biopsy. Cancer Immunol Immunother, 2021, 70(5): 1177-1188.
4. 周彩存, 王洁, 王宝成, 等. 中国非小细胞肺癌免疫检查点抑制剂治疗专家共识(2020年版). 中国肺癌杂志, 2021, 24(4): 217-235.
5. 王亚东, 杨笑盈, 贾梓淇, 等. 循环肿瘤细胞PD-L1表达在非小细胞肺癌免疫治疗中的应用. 中国胸心血管外科临床杂志, 2021, 28(1): 110-115.
6. Liberini V, Mariniello A, Righi L, et al. NSCLC biomarkers to predict response to immunotherapy with checkpoint inhibitors (ICI): From the cells to in vivo images. Cancers (Basel), 2021, 13(18): 4543.
7. Chen C. A glimpse of the first eight months of the COVID-19 literature on microsoft academic graph: Themes, citation contexts, and uncertainties. Front Res Metr Anal, 2020, 5: 607286.
8. 张雨, 徐燕, 崔倩, 等. 基于Web of Science的国外免疫检查点抑制剂在肺癌治疗中应用的研究现状及热点分析. 现代肿瘤医学, 2022, 30(5): 891-895.
9. Goodman AM, Kato S, Bazhenova L, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther, 2017, 16(11): 2598-2608.
10. Kamphorst AO, Pillai RN, Yang S, et al. Proliferation of PD-1+ CD8 T cells in peripheral blood after PD-1-targeted therapy in lung cancer patients. Proc Natl Acad Sci U S A, 2017, 114(19): 4993-4998.
11. Bagley SJ, Kothari S, Aggarwal C, et al. Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung Cancer, 2017, 106: 1-7.
12. Trebeschi S, Drago SG, Birkbak NJ, et al. Predicting response to cancer immunotherapy using noninvasive radiomic biomarkers. Ann Oncol, 2019, 30(6): 998-1004.
13. Sun J, Zhang Z, Bao S, et al. Identification of tumor immune infiltration-associated lncRNAs for improving prognosis and immunotherapy response of patients with non-small cell lung cancer. J Immunother Cancer, 2020, 8(1): e000110.
14. Del Re M, Marconcini R, Pasquini G, et al. PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC. Br J Cancer, 2018, 118(6): 820-824.
15. Aguiar PN, De Mello RA, Hall P, et al. PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: Updated survival data. Immunotherapy, 2017, 9(6): 499-506.
16. Prelaj A, Tay R, Ferrara R, et al. Predictive biomarkers of response for immune checkpoint inhibitors in non-small-cell lung cancer. Eur J Cancer, 2019, 106: 144-159.
17. Xia L, Liu Y, Wang Y. PD-1/PD-L1 blockade therapy in advanced non-small-cell lung cancer: Current status and future directions. Oncologist, 2019, 24(Suppl 1): S31-S41.
18. Malhotra J, Jabbour SK, Aisner J. Current state of immunotherapy for non-small cell lung cancer. Transl Lung Cancer Res, 2017, 6(2): 196-211.
19. Hanna NH, Robinson AG, Temin S, et al. Therapy for stage Ⅳ non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol, 2021, 39(9): 1040-1091.
20. Yu Y, Zeng D, Ou Q, et al. Association of survival and immune-related biomarkers with immunotherapy in patients with non-small cell lung cancer: A meta-analysis and individual patient-level analysis. JAMA Netw Open, 2019, 2(7): e196879.
21. Havel JJ, Chowell D, Chan TA. The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy. Nat Rev Cancer, 2019, 19(3): 133-150.
22. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med, 2018, 378(22): 2093-2104.
23. Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: Prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol, 2020, 21(10): 1353-1365.
24. Litchfield K, Reading JL, Puttick C, et al. Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell, 2021, 184(3): 596-614.
25. 方涛, 雷想, 宋兵. 阿特珠单抗在肺癌治疗中的研究进展. 中国胸心血管外科临床杂志, 2022, 29(1): 114-120.
26. Lei X, Lei Y, Li JK, et al. Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy. Cancer Lett, 2020, 470: 126-133.
27. Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 2014, 515(7528): 563-567.
28. Sliker BH, Campbell PM. Fibroblasts influence the efficacy, resistance, and future use of vaccines and immunotherapy in cancer treatment. Vaccines (Basel), 2021, 9(6): 634.
29. Barrett RL, Puré E. Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy. Elife, 2020, 9: e57243.
30. Guibert N, Delaunay M, Lusque A, et al. PD-L1 expression in circulating tumor cells of advanced non-small cell lung cancer patients treated with nivolumab. Lung Cancer, 2018, 120: 108-112.
31. Boffa DJ, Graf RP, Salazar MC, et al. Cellular expression of PD-L1 in the peripheral blood of lung cancer patients is associated with worse survival. Cancer Epidemiol Biomarkers Prev, 2017, 26(7): 1139-1145.
32. Ilié M, Szafer-Glusman E, Hofman V, et al. Detection of PD-L1 in circulating tumor cells and white blood cells from patients with advanced non-small-cell lung cancer. Ann Oncol, 2018, 29(1): 193-199.
33. Cabel L, Riva F, Servois V, et al. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: A proof-of-concept study. Ann Oncol, 2017, 28(8): 1996-2001.
34. Giroux Leprieur E, Herbretau G, Dumenil C, et al. Circulating tumor DNA evaluated by next-generation sequencing is predictive of tumor response and prolonged clinical benefit with nivolumab in advanced non-small cell lung cancer. Oncoimmunology, 2018, 7(5): e1424675.
35. Goldberg SB, Narayan A, Kole AJ, et al. Early assessment of lung cancer immunotherapy response via circulating tumor DNA. Clin Cancer Res, 2018, 24(8): 1872-1880.
36. Alama A, Coco S, Genova C, et al. Prognostic relevance of circulating tumor cells and circulating cell-free DNA association in metastatic non-small cell lung cancer treated with nivolumab. J Clin Med, 2019, 8(7): 1011.
37. Pasini L, Ulivi P. Liquid biopsy for the detection of resistance mechanisms in NSCLC: Comparison of different blood biomarkers. J Clin Med, 2019, 8(7): 998.
38. Jiang T, Bai Y, Zhou F, et al. Clinical value of neutrophil-to-lymphocyte ratio in patients with non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors. Lung Cancer, 2019, 130: 76-83.
39. Möller M, Turzer S, Schütte W, et al. Blood immune cell biomarkers in patient with lung cancer undergoing treatment with checkpoint blockade. J Immunother, 2020, 43(2): 57-66.
40. Pasini L, Ulivi P. Extracellular vesicles in non-small-cell lung cancer: Functional role and involvement in resistance to targeted treatment and immunotherapy. Cancers (Basel), 2019, 12(1): 40.
41. Wu J, Li S, Zhang P. Tumor-derived exosomes: Immune properties and clinical application in lung cancer. Cancer Drug Resist, 2022, 5(1): 102-113.
42. Li C, Li C, Zhi C, et al. Clinical significance of PD-L1 expression in serum-derived exosomes in NSCLC patients. J Transl Med, 2019, 17(1): 355.
43. Wang JH, Wahid KA, van Dijk LV, et al. Radiomic biomarkers of tumor immune biology and immunotherapy response. Clin Transl Radiat Oncol, 2021, 28: 97-115.
44. Wang H, Chen YZ, Li WH, et al. Pretreatment thoracic CT radiomic features to predict brain metastases in patients with ALK-rearranged non-small cell lung cancer. Front Genet, 2022, 13: 772090.
45. 徐嘉昕, 钱凯, 蒋立虹. 机器学习算法在肺癌临床诊断及生存预后分析中的应用. 中国胸心血管外科临床杂志, 2022, 29(6): 777-781.
46. Piñeiro-Fiel M, Moscoso A, Pubul V, et al. A systematic review of PET textural analysis and radiomics in cancer. Diagnostics (Basel), 2021, 11(2): 380.
47. Jiang M, Sun D, Guo Y, et al. Assessing PD-L1 expression level by radiomic features from PET/CT in nonsmall cell lung cancer patients: An initial result. Acad Radiol, 2020, 27(2): 171-179.
48. Valentinuzzi D, Vrankar M, Boc N, et al. [18F]FDG PET immunotherapy radiomics signature (iRADIOMICS) predicts response of non-small-cell lung cancer patients treated with pembrolizumab. Radiol Oncol, 2020, 54(3): 285-294.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Frontier and hotspot of biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer

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