Circulating white blood cells and risk of tonsillar and base of tongue squamous cell carcinoma: A retrospective and mendelian randomization study.
Leucocitos circulantes y riesgo de carcinoma de células escamosas de amígdalas y base de la lengua: un estudio retrospectivo y de aleatorización mendeliana.
Palabras clave:
Neoplasias Tonsilares, Leucocitos, Análisis de la Aleatorización Mendeliana, Virus del Papiloma Humano, Carcinoma de Células Escamosas de Cabeza y Cuello
Resumen
Este estudio tuvo como objetivo explorar la relación entre los leucocitos circulantes (LC) y el riesgo de carcinoma de células escamosas de amígdala y de base de la lengua (CCEA/CCEB), mediante datos clínicos retrospectivos y análisis de aleatorización mendeliana (AM). Se analizó una cohorte retrospectiva de 239 pacientes con CCEA/CCEB para determinar los subtipos de LC y su asociación con variables clínico-patológicas, estratificadas según el estado del virus del papiloma humano (VPH). Se incluyeron análisis de sangre, estadificación tumoral y marcado- res inmunológicos. Para la inferencia causal, se realizó un análisis de AM utilizando datos del estudio de asociación del genoma completo (GWAS) sobre LC del Con- sorcio de Células Sanguíneas (Biobanco del Reino Unido) y datos de resultados de CCEA/CCEB del consorcio FinnGen. Los polimorfismos de un nucleótido (SNP) se seleccionaron en función de su significancia a nivel genómico (p<5 × 10⁻⁸), bajo desequilibrio de ligamiento (r² <0,001) y un estadístico F >10. Se utilizó la ponderación por el inverso de la varianza (IVW: Inverse Variance Weighted) como método principal de AM, complementado con análisis de regresión MR-Egger, mediana ponderada y moda ponderada. El análisis retrospectivo reveló diferencias significativas en los subtipos de leucocitos totales (LCt) según el sexo, la edad, los factores del estilo de vida y el estado del VPH. Cabe destacar que los neutrófilos y monocitos se asociaron fuertemente con el estadio tumoral y los marcadores inmunitarios. El análisis de AM confirmó una asociación causal entre el recuento total de LC y el riesgo de carcinoma de células escamosas de la lengua/base de la vejiga (OR=1,516, p=0,005), sin evidencia de heterogeneidad ni pleiotropía. No se encontró ningún vínculo causal entre los subtipos de LC y otros sitios de carcinoma de células escamosas de cabeza y cuello. Este estudio proporciona la primera evidencia integrada que respalda un papel causal de los LC elevados en la patogénesis del CCEA/CCEB. Estos hallazgos sugieren que el recuento de leucocitos en sangre periférica (LC) podría servir como biomarcador y objetivo terapéutico en el carcinoma de células escamosas de la lengua/base de la lengua (CCEA/CCEB), relacionado o no con el VPH.
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Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, 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. https://doi.org/10.3322/caac.21660g
Arif RT, Mogaddam MA, Merdad LA, Farsi NJ. Does human papillomavirus modify the risk of oropharyngeal cancer related to smoking and alcohol drinking? A systematic review and meta-analysis. Laryngoscope Investig Otolaryngol. 2022;7(5):1391-1401. https://doi.org/10.1002/lio2.877.
Ernster JA, Sciotto CG, O'Brien MM, Finch JL, Robinson LJ, Willson T, et al. Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus. Laryngoscope. 2007;117(12):2115-2128. https://doi.org/10.1097/MLG.0b013e31813e5fbb.
Licitra L, Zigon G, Gatta G, Sánchez MJ, Berrino F, EUROCARE Working Group. Human papillomavirus in HNSCC: a European epidemiologic perspective. Hematol Oncol Clin North Am. 2008;22(6):1143-1153, vii-viii. https://doi.org/10.1016/j.hoc.2008.10.002.
Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008;26(4):612-619. https://doi.org/10.1200/JCO.2007.14. 1713.
Zoschke IN, Bennis SL, Wilkerson JM, Stull CL, Nyitray AG, Khariwala SS, et al. HPV-related oropharyngeal cancer early detection in gay and bisexual men is an "orphan": A qualitative analysis among healthcare providers. Front Public Health. 2023;11:1165107. https://doi.org/10.3389/fpubh.2023.1165107.
Shi T, Hu Z, Tian L, Yang Y. Pan-cancer landscape of CENPO and its underlying mechanism in LUAD. Respir Res. 2023;24(1):113. https://doi.org/10.1186/12931-023-02408-3.
Chechlinska M, Kowalewska M, Nowak R. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Nat Rev Cancer. 2010;10(1):2-3. https://doi.org/10.1038/nrc2782.
Thol K, Pawlik P, MeGranahan N. Therapy sculpts the complex interplay between cancer and the immune system during tumour evolution. Genome Med. 2022;14(1):137. https://doi.org/10.1186/s13073-022-01138-3.
Wang Y, Jiang H, Fu L, Guan L, Yang J, Ren J, et al. Prognostic value and immunological role of PD-L1 gene in pan-cancer. BMC Cancer. 2024;24(1):20. https://doi.org/10.1186/s12885-023-11267-6.
Xu J, Liu H, Wang T, Wen Z, Chen H, Yang Z, et al. CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy. Adv Sci (Weinh). 2023:10(17):e2207017. https://doi.org/10.1002/advs.202207017.
Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167. https://doi.org/10.1016/S0140-6736(18)31999-8.
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. https://doi.org/10.1016/S0140-6736(19)32591-7.
Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6(1):149-163. https://doi.org/10.2217/fon.09.136.
Aoki H, Ueha S, Shichino S, Ogiwara H, Hashimoto SI, Kakimi K, et al. TCR Repertoire Analysis Reveals Mobilization of Novel CD8+ T Cell Clones into the Cancer-Immunity Cycle Following Anti-CD4 Antibody Administration. Front Immunol. 2019:9:3185. https://doi.org/10.3389/fimmu. 2018.03185.
Chen MH, Raffield LM, Mousas A, Sakaue S, Huffman JE, Moscati A, et al. Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations. Cell. 2020;182(5):1198-1213.e14. https://doi.org/10.1016/j.cell.2020.06.045.
Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner KM, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023:613(7944):508-518. https://doi.org/10.1038/s41586-022-05473-8.
Bowden J, Del Greco M F, Minelli C, Zhao Q, Lawlor DA, Sheehan NA, et al. Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption. Int J Epidemiol. 2019;48(3):728-742. https://doi.org/10.1093/ije/dyy258.
Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:234408. https://doi.org/10.7554/eLife.34408.
Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32(5):377-389. https://doi.org/10.1007/s10654-017-0276-5.
Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294-4301. https://doi.org/10.1200/JCO.2011. 36.4596.
Pytynia KB, Dahlstrom KR, Sturgis EM. Epidemiology of HPV-associated oropharyngeal cancer. Oral Oncol. 2014;50(5):380-386. https://doi.org/10.1016/j.oraloncology.2013.12.019.
Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015 33(29):3235-3242. https://doi.org/10.1200/JCO.2015.61.6995.
Wei D, Liu J, Ma J. The value of lymphocyte to monocyte ratio in the prognosis of head and neck squamous cell carcinoma: a meta-analysis. PeerJ. 2023;11:e16014. https://doi.org/10.7717/peerj.16014.
Camargo S, Moskowitz O, Giladi A, Levinson M, Balaban R, Gola S, et al. Neutrophils physically interact with tumour cells to form a signaling niche promoting breast cancer aggressiveness. Nat Cancer, 2025;6(3):540-558, https://doi.org/10.1038/s43018-025-00924-3
Hurtado Gutiérrez MJ, Allard FL, Mosha HT, Dubois CM, McDonald PP. Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses. Cells. 2022;12(1):136. https://doi.org/10.3390/cells12010136.
Ng M, Cerezo-Wallis D, Ng LG, Hidalgo A. Adaptations of neutrophils in cancer. Immunity. 2025;58(1):40-58. https://doi.org/10.1016/j.immuni.2024.12.009.
Li Q, Xiao Y, Han L, Luo W, Dai W, Fang IH, et al. Microbiome dysbiosis, neutrophil recruitment and mesenchymal transition of mesothelial cells promotes peritoneal metastasis of colorectal cancer. Nat Cancer. 2025;6(3):493-510. https://doi.org/10.1038/s43018-025-00910-9.
Tham T, Bardash Y, Herman SW, Costantino PD. Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: A systematic review and meta-analysis. Head Neck. 2018;40(11):2546-2557. https://doi.org/10.1002/hed.25324.
Tan LY, Cockshell MP, Moore E, Myo Min KK, Ortiz M, Johan MZ, et al. Vasculogenic mimicry structures in melanoma support the recruitment of monocytes. Oncoimmunology. 2022;11(1):2043673. https://doi.org/10.1080/2162402X.2022.2043673.
Wang J, Gai J, Zhang T, Niu N, Qi H, Thomas DL 2nd, et al. Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumour cells.. Sei Adv. 2024;10(6):eadk1827. https://doi.org/10.1126/sciadv.adk1827.
Kim MJ, Hong SPD, Park Y, Chae YK. Incidence of immunotherapy-related hyperprogressive disease (HPD) across HPD definitions and cancer types in observational studies: A systematic review and meta-analysis. Cancer Med. 2024;13(3):e6970. https://doi.org/10.1002/cam4.6970.
Liu Y, Wu X, Feng Y, Jiang Q, Zhang S, Wang Q, et al. Insights into the Oncogenic, Prognostic, and Immunological Role of BRIP1 in Pan-Cancer: A Comprehensive Data-Mining-Based Study. J Oncol. 2023;2023:4104639. https://doi.org/10.1155/2023/4104639.
Ilié M, Szafer-Glusman E, Hofman V, Chamorey E, Lalvée S, Selva E, et al. Detection of PD-L1 in circulating tumour cells and white blood cells from patients with advanced non-small-cell lung cancer, Ann Oncol. 2018;29(1):193-199. https://doi.org/10.1093/annone/mdx636.
van Rossum PSN, Deng W, Routman DM, Liu AY, Xu C, Shiraishi Y, et al. Prediction of Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Development and Validation of a Pretreatment Nomogram. Pract Radiat Oncol. 2020;10(1):e16-e26. https://doi.org/10.1016/j.prro.2019.07.010.
Gungabeesoon J, Gort-Freitas NA, Kiss M, Weissleder R, Klein AM, Pittet MJ, et al. A neutrophil response linked to tumour control in immunotherapy. Cell. 2023 186(7):1448-1464.e20. https://doi.org/10.1016/j.cell.2023.02.032.
Xu F, Xu P, Cui W, Gong W, Wei Y, Liu B, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may aid in identifying patients with non-small cell lung cancer and predicting Tumour-Node-Metastasis stages. Oncol Lett. 2018;16(1):483-490. https://doi.org/10.3892/ol.2018.8644.
Diehl A, Yarchoan M, Hopkins A, Jaffee E, Grossman SA. Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumours treated with PD-1 checkpoint inhibitors. Oncotarget. 2017;8(69):114268-114260. https://doi.org/10.18632/oncotarget.23217.
Liu W, Liu Y, Ma F, Sun B, Wang Y, Luo J, et. al. Peripheral Blood Markers Associated with Immune-Related Adverse Effects in Patients Who Had Advanced Non-Small Cell Lung Cancer Treated with PD-1 Inhibitors. Cancer Manag Res. 2021; 13:765-771. https://doi.org/10.2147/CMAR.S29 3200.
Michailidou D, Khaki AR, Morelli MP, Diamantopoulos L, Singh N, Grivas P. Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors. Sei Rep. 2021 11(1):9029. https://doi.org/10.1038/s41598-021-88307-3.
Devalaraja S, To TKJ, Folkert IW, Natesan R, Alam MZ, Li M, et al. Tumour-Derived Retinoic Acid Regulates Intratumoural Monocyte Differentiation to Promote Immune Suppression. Cell. 2020;180(6):1098-1114.e16. https://doi.org/10.1016/j.cell. 2020.02.042.
Olingy CE, Dinh HQ, Hedrick CC. Monocyte heterogeneity and functions in cancer. J Leukoc Biol. 2019;106(2):309-322. https://doi.org/10.1002/JLB.4RI0818-311R.
Arif RT, Mogaddam MA, Merdad LA, Farsi NJ. Does human papillomavirus modify the risk of oropharyngeal cancer related to smoking and alcohol drinking? A systematic review and meta-analysis. Laryngoscope Investig Otolaryngol. 2022;7(5):1391-1401. https://doi.org/10.1002/lio2.877.
Ernster JA, Sciotto CG, O'Brien MM, Finch JL, Robinson LJ, Willson T, et al. Rising incidence of oropharyngeal cancer and the role of oncogenic human papilloma virus. Laryngoscope. 2007;117(12):2115-2128. https://doi.org/10.1097/MLG.0b013e31813e5fbb.
Licitra L, Zigon G, Gatta G, Sánchez MJ, Berrino F, EUROCARE Working Group. Human papillomavirus in HNSCC: a European epidemiologic perspective. Hematol Oncol Clin North Am. 2008;22(6):1143-1153, vii-viii. https://doi.org/10.1016/j.hoc.2008.10.002.
Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008;26(4):612-619. https://doi.org/10.1200/JCO.2007.14. 1713.
Zoschke IN, Bennis SL, Wilkerson JM, Stull CL, Nyitray AG, Khariwala SS, et al. HPV-related oropharyngeal cancer early detection in gay and bisexual men is an "orphan": A qualitative analysis among healthcare providers. Front Public Health. 2023;11:1165107. https://doi.org/10.3389/fpubh.2023.1165107.
Shi T, Hu Z, Tian L, Yang Y. Pan-cancer landscape of CENPO and its underlying mechanism in LUAD. Respir Res. 2023;24(1):113. https://doi.org/10.1186/12931-023-02408-3.
Chechlinska M, Kowalewska M, Nowak R. Systemic inflammation as a confounding factor in cancer biomarker discovery and validation. Nat Rev Cancer. 2010;10(1):2-3. https://doi.org/10.1038/nrc2782.
Thol K, Pawlik P, MeGranahan N. Therapy sculpts the complex interplay between cancer and the immune system during tumour evolution. Genome Med. 2022;14(1):137. https://doi.org/10.1186/s13073-022-01138-3.
Wang Y, Jiang H, Fu L, Guan L, Yang J, Ren J, et al. Prognostic value and immunological role of PD-L1 gene in pan-cancer. BMC Cancer. 2024;24(1):20. https://doi.org/10.1186/s12885-023-11267-6.
Xu J, Liu H, Wang T, Wen Z, Chen H, Yang Z, et al. CCR7 Mediated Mimetic Dendritic Cell Vaccine Homing in Lymph Node for Head and Neck Squamous Cell Carcinoma Therapy. Adv Sci (Weinh). 2023:10(17):e2207017. https://doi.org/10.1002/advs.202207017.
Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156-167. https://doi.org/10.1016/S0140-6736(18)31999-8.
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-1928. https://doi.org/10.1016/S0140-6736(19)32591-7.
Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6(1):149-163. https://doi.org/10.2217/fon.09.136.
Aoki H, Ueha S, Shichino S, Ogiwara H, Hashimoto SI, Kakimi K, et al. TCR Repertoire Analysis Reveals Mobilization of Novel CD8+ T Cell Clones into the Cancer-Immunity Cycle Following Anti-CD4 Antibody Administration. Front Immunol. 2019:9:3185. https://doi.org/10.3389/fimmu. 2018.03185.
Chen MH, Raffield LM, Mousas A, Sakaue S, Huffman JE, Moscati A, et al. Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations. Cell. 2020;182(5):1198-1213.e14. https://doi.org/10.1016/j.cell.2020.06.045.
Kurki MI, Karjalainen J, Palta P, Sipilä TP, Kristiansson K, Donner KM, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023:613(7944):508-518. https://doi.org/10.1038/s41586-022-05473-8.
Bowden J, Del Greco M F, Minelli C, Zhao Q, Lawlor DA, Sheehan NA, et al. Improving the accuracy of two-sample summary-data Mendelian randomization: moving beyond the NOME assumption. Int J Epidemiol. 2019;48(3):728-742. https://doi.org/10.1093/ije/dyy258.
Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:234408. https://doi.org/10.7554/eLife.34408.
Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol. 2017;32(5):377-389. https://doi.org/10.1007/s10654-017-0276-5.
Chaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294-4301. https://doi.org/10.1200/JCO.2011. 36.4596.
Pytynia KB, Dahlstrom KR, Sturgis EM. Epidemiology of HPV-associated oropharyngeal cancer. Oral Oncol. 2014;50(5):380-386. https://doi.org/10.1016/j.oraloncology.2013.12.019.
Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of Human Papillomavirus-Positive Head and Neck Squamous Cell Carcinoma. J Clin Oncol. 2015 33(29):3235-3242. https://doi.org/10.1200/JCO.2015.61.6995.
Wei D, Liu J, Ma J. The value of lymphocyte to monocyte ratio in the prognosis of head and neck squamous cell carcinoma: a meta-analysis. PeerJ. 2023;11:e16014. https://doi.org/10.7717/peerj.16014.
Camargo S, Moskowitz O, Giladi A, Levinson M, Balaban R, Gola S, et al. Neutrophils physically interact with tumour cells to form a signaling niche promoting breast cancer aggressiveness. Nat Cancer, 2025;6(3):540-558, https://doi.org/10.1038/s43018-025-00924-3
Hurtado Gutiérrez MJ, Allard FL, Mosha HT, Dubois CM, McDonald PP. Human Neutrophils Generate Extracellular Vesicles That Modulate Their Functional Responses. Cells. 2022;12(1):136. https://doi.org/10.3390/cells12010136.
Ng M, Cerezo-Wallis D, Ng LG, Hidalgo A. Adaptations of neutrophils in cancer. Immunity. 2025;58(1):40-58. https://doi.org/10.1016/j.immuni.2024.12.009.
Li Q, Xiao Y, Han L, Luo W, Dai W, Fang IH, et al. Microbiome dysbiosis, neutrophil recruitment and mesenchymal transition of mesothelial cells promotes peritoneal metastasis of colorectal cancer. Nat Cancer. 2025;6(3):493-510. https://doi.org/10.1038/s43018-025-00910-9.
Tham T, Bardash Y, Herman SW, Costantino PD. Neutrophil-to-lymphocyte ratio as a prognostic indicator in head and neck cancer: A systematic review and meta-analysis. Head Neck. 2018;40(11):2546-2557. https://doi.org/10.1002/hed.25324.
Tan LY, Cockshell MP, Moore E, Myo Min KK, Ortiz M, Johan MZ, et al. Vasculogenic mimicry structures in melanoma support the recruitment of monocytes. Oncoimmunology. 2022;11(1):2043673. https://doi.org/10.1080/2162402X.2022.2043673.
Wang J, Gai J, Zhang T, Niu N, Qi H, Thomas DL 2nd, et al. Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumour cells.. Sei Adv. 2024;10(6):eadk1827. https://doi.org/10.1126/sciadv.adk1827.
Kim MJ, Hong SPD, Park Y, Chae YK. Incidence of immunotherapy-related hyperprogressive disease (HPD) across HPD definitions and cancer types in observational studies: A systematic review and meta-analysis. Cancer Med. 2024;13(3):e6970. https://doi.org/10.1002/cam4.6970.
Liu Y, Wu X, Feng Y, Jiang Q, Zhang S, Wang Q, et al. Insights into the Oncogenic, Prognostic, and Immunological Role of BRIP1 in Pan-Cancer: A Comprehensive Data-Mining-Based Study. J Oncol. 2023;2023:4104639. https://doi.org/10.1155/2023/4104639.
Ilié M, Szafer-Glusman E, Hofman V, Chamorey E, Lalvée S, Selva E, et al. Detection of PD-L1 in circulating tumour cells and white blood cells from patients with advanced non-small-cell lung cancer, Ann Oncol. 2018;29(1):193-199. https://doi.org/10.1093/annone/mdx636.
van Rossum PSN, Deng W, Routman DM, Liu AY, Xu C, Shiraishi Y, et al. Prediction of Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Development and Validation of a Pretreatment Nomogram. Pract Radiat Oncol. 2020;10(1):e16-e26. https://doi.org/10.1016/j.prro.2019.07.010.
Gungabeesoon J, Gort-Freitas NA, Kiss M, Weissleder R, Klein AM, Pittet MJ, et al. A neutrophil response linked to tumour control in immunotherapy. Cell. 2023 186(7):1448-1464.e20. https://doi.org/10.1016/j.cell.2023.02.032.
Xu F, Xu P, Cui W, Gong W, Wei Y, Liu B, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may aid in identifying patients with non-small cell lung cancer and predicting Tumour-Node-Metastasis stages. Oncol Lett. 2018;16(1):483-490. https://doi.org/10.3892/ol.2018.8644.
Diehl A, Yarchoan M, Hopkins A, Jaffee E, Grossman SA. Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumours treated with PD-1 checkpoint inhibitors. Oncotarget. 2017;8(69):114268-114260. https://doi.org/10.18632/oncotarget.23217.
Liu W, Liu Y, Ma F, Sun B, Wang Y, Luo J, et. al. Peripheral Blood Markers Associated with Immune-Related Adverse Effects in Patients Who Had Advanced Non-Small Cell Lung Cancer Treated with PD-1 Inhibitors. Cancer Manag Res. 2021; 13:765-771. https://doi.org/10.2147/CMAR.S29 3200.
Michailidou D, Khaki AR, Morelli MP, Diamantopoulos L, Singh N, Grivas P. Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors. Sei Rep. 2021 11(1):9029. https://doi.org/10.1038/s41598-021-88307-3.
Devalaraja S, To TKJ, Folkert IW, Natesan R, Alam MZ, Li M, et al. Tumour-Derived Retinoic Acid Regulates Intratumoural Monocyte Differentiation to Promote Immune Suppression. Cell. 2020;180(6):1098-1114.e16. https://doi.org/10.1016/j.cell. 2020.02.042.
Olingy CE, Dinh HQ, Hedrick CC. Monocyte heterogeneity and functions in cancer. J Leukoc Biol. 2019;106(2):309-322. https://doi.org/10.1002/JLB.4RI0818-311R.
Publicado
2026-05-31
Cómo citar
Zhu, C., He, S., Li, Z., Shi, Y., Zhao, J., & Li, W. (2026). Circulating white blood cells and risk of tonsillar and base of tongue squamous cell carcinoma: A retrospective and mendelian randomization study.: Leucocitos circulantes y riesgo de carcinoma de células escamosas de amígdalas y base de la lengua: un estudio retrospectivo y de aleatorización mendeliana. Investigación Clínica, 67(2), 260-274. https://doi.org/10.54817/IC.v67n2a08
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