|Table of Contents|

Correlation of peripheral blood PD-1,CTLA-4,T-reg,pDC with clinical characteristics and efficacy of nasopharyngeal carcinoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 01
Page:
53-60
Research Field:
Publishing date:

Info

Title:
Correlation of peripheral blood PD-1,CTLA-4,T-reg,pDC with clinical characteristics and efficacy of nasopharyngeal carcinoma
Author(s):
XU Xinyu1; 2; 3; ZHAO Chaofen1; 2; HE Qianyong1; 2; 3; LIU Lina1; 2; 3; WANG Wei4; SHAO Chunyan4; XIONG Wei4; JIN Feng1; 2; 3
1.Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guizhou Guiyang 550004，China; 2.Department of Oncology；4. Department of Clinical Laboratory, Affiliated Cancer Hospital of Guizhou Medical University, Guizhou Guiyang 550008，China; 3.Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guizhou Guiyang 550004，China.
Keywords:
nasopharyngeal carcinoma; clinical characteristics; curative effect; PD-1; CTLA-4; T-reg; pDC
PACS:
R739.62
DOI:
10.3969/j.issn.1672-4992.2024.01.009
Abstract:
Objective:To explore the relationship between peripheral blood PD-1/CTL(%),CTLA-4/CTL(%),T-reg(%),pDC and the clinical characteristics and immediate curative effect of nasopharyngeal carcinoma in patients with primary treatment of nasopharyngeal carcinoma before treatment,as well as the expression difference in patients with nasopharyngeal carcinoma and healthy people.Methods:The clinical data,lymphocyte subsets and dendritic cell subsets of 112 patients with initially treated nasopharyngeal carcinoma were collected before treatment,and the correlation between peripheral blood PD-1/CTL(%),CTLA-4/CTL(%),T-reg(%),pDC and the clinical characteristics and immediate efficacy of nasopharyngeal carcinoma was analyzed.In 112 patients with nasopharyngeal carcinoma,30 patients were randomly selected as the case group,and 30 healthy patients matched in age and gender were selected as the control group.The expression differences of PD-1/CTL(%),CTLA-4/CTL(%),T-reg(%) and pDC in peripheral blood of the two groups were analyzed.Results:Among 112 patients with nasopharyngeal carcinoma treated for the first time,PD-1/CTL(%) in peripheral blood of ≥50 years old group was higher than that of <50 years old group.CTLA-4/CTL(%) was negatively correlated with T stage,N stage and TNM stage.The higher the CTLA-4/CT(%),the better the therapeutic effect.T-reg(%) was positively correlated with N staging.T-reg(%) had an S-type curve relationship with M stage.pDC was negatively correlated with N stage and TNM stage.There was statistical significance in PD-1/CTL(%) and T-reg(%) of peripheral blood between the case group and the control group,while there was no statistical significance in CTLA-4/CTL(%) of peripheral blood between the case group and the control group.Conclusion:The higher the peripheral blood CTLA-4/CT(%),the earlier the T stage,N stage and TNM stage of nasopharyngeal carcinoma.The higher the peripheral blood CTLA-4/CT(%),the better the curative effect.The higher the T-reg(%) in peripheral blood,the later the N stage.When peripheral blood T-reg(%)<20%,nasopharyngeal carcinoma may not have distant metastasis.When peripheral blood T-reg(%) was 20%~50%,the expression of peripheral blood T-reg(%) is higher,the possibility of distant metastasis is greater.When peripheral blood T-reg(%)>50%,the possibility of distant metastasis of nasopharyngeal carcinoma is greater.The higher the pDC of peripheral blood,the earlier the N stage and the TNM stage.The indexes above peripheral blood can be dynamically observed,which are expected to become the biomarkers to predict the efficacy and prognosis of patients with nasopharyngeal carcinoma.

References:

[1]AU KH,NGAN RKC,NG AWY,et al.Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity modulated radiotherapy(IMRT) in Hong Kong:A report of 3328 patients(HKNPCSG 1301 study)［J］.Oral Oncology,2018,77:16-21.
[2]CHEN L,ZHANG Y,LAI SZ,et al.10-year results of therapeutic ratio by intensity-modulated radiotherapy versus two-dimensional radiotherapy in patients with nasopharyngeal carcinoma［J］.The Oncologist,2019,24(1):e38-e45.
[3]CHAN OS,NGAN RKC.Individualized treatment in stage IVC nasopharyngeal carcinoma［J］.Oral Oncology,2014,50(9):791-797.
[4]ZHANG MX,LI J,SHEN GP,et al.Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy:A 10-year experience with a large cohort and long follow-up［J］.European Journal of Cancer(Oxford,England:1990),2015,51(17):2587-2595.
[5]HUANG R,CHEN K,JIANG Y,et al.Development of prognostic nomogram based on lipid metabolic markers and lactate dehydrogenase in non-metastatic nasopharyngeal carcinoma［J］.Journal of Inflammation Research,2023,16:3093-3107.
[6]SECONDINO S,PEDRAZZOLI P,BASSO S,et al.Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma［J］.Frontiers in Immunology,2023,14:1208475.
[7]MAO YP,TANG LL,CHEN L,et al.Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy［J］.Chinese Journal of Cancer,2016,35(1):103.
[8]ALDHAHRI SF,AARAKEH MM,ALMETARY RJ,et al.Patterns of treatment failure in patients with nasopharyngeal carcinoma and salvage treatment outcome:A retrospective analysis study［J］.American Journal of Otolaryngology,2023,44(5):103941.
[9]COHEN E,BELL RB,BIFULCO CB,et al.The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck(HNSCC)［J］.Journal for Immunotherapy of Cancer,2019,7(1):184.
[10]ZHANG L,HUANG Y,HONG S,et al.Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma:a multicentre,randomised,open-label,phase 3 trial［J］.Lancet,2016,388(10054):1883-1892.
[11]HSU C,LEE SH,EJADI S,et al.Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1-positive nasopharyngeal carcinoma:Results of the KEYNOTE-028 Study［J］.Journal of Clinical Oncology,2017,35(36):4050-4056.
[12]MA B,LIM WT,GOH BC,et al.Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma:An international,multicenter study of the mayo clinic phase 2 consortium(NCI-9742)［J］.Journal of Clinical Oncology,2018,36(14):1412-1418.
[13]FANG W,YANG Y,MA Y,et al.Camrelizumab(SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma:results from two single-arm,phase 1 trials［J］.The Lancet Oncology,2018,19(10):1338-1350.
[14]WANG FH,WEI XL,FENG J,et al.Efficacy,safety,and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma:A phase II clinical trial(POLARIS-02)［J］.Journal of Clinical Oncology,2021,39(7):704-712.
[15]PENNOCK GK,CHOW LQ.The evolving role of immune checkpoint inhibitors in cancer treatment［J］.The Oncologist,2015,20(7):812-822.
[16]HAU PM,LUNG HL,WU M,et al.Targeting epstein-barr virus in nasopharyngeal carcinoma［J］.Frontiers in Oncology,2020,10:600.
[17]SU ZY,SIAK PY,LEONG CO,et al.Nasopharyngeal carcinoma and its microenvironment:Past,current,and future perspectives［J］.Frontiers in Oncology,2022,12:840467.
[18]GIOVANELLI P,SANDOVAL TA,CUBILLOS-RUIZ JR.Dendritic cell metabolism and function in tumors［J］.Trends in Immunology,2019,40(8):699-718.
[19]HUANG PY,GUO SS,ZHANG Y,et al.Tumor CTLA-4 overexpression predicts poor survival in patients with nasopharyngeal carcinoma［J］.Oncotarget,2016,7(11):13060-13068.
[20]VILLANI AC,SATIJA R,REYNOLDS G,et al.Single-cell RNA-seq reveals new types of human blood dendritic cells,monocytes,and progenitors［J］.Science,2017,356(6335):eaah4573.
[21]WAISMAN A,LUKAS D,CLAUSEN BE,et al.Dendritic cells as gatekeepers of tolerance［J］.Seminars in Immunopathology,2017,39(2):153-163.
[22]AHMED MM,GEBRIEL MG,MORAD EA,et al.Expression of immune checkpoint regulators,cytotoxic T-lymphocyte antigen-4,and programmed death-ligand 1 in epstein-barr virus-associated nasopharyngeal carcinoma［J］.Applied Immunohistochemistry & Molecular Morphology,2021,29(6):401-408.
[23]CHEN YP,CHAN A,LE QT,et al.Nasopharyngeal carcinoma［J］.Lancet,2019,394(10192):64-80.
[24]ZHOU Y,SHI D,MIAO J,et al.PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load［J］.Scientific Reports,2017,7:43627.
[25]KLOTZ R,THOMAS A,TENG T,et al.Circulating tumor cells exhibit metastatic tropism and reveal brain metastasis drivers［J］.Cancer Discovery,2020,10(1):86-103.
[26]ZENG F,LU T,XIE F,et al.Effects of locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma:A real-world study［J］.Translational Oncology,2021,14(11):101187.
[27]MAHONEY KM,RENNERT PD,FREEMAN GJ.Combination cancer immunotherapy and new immunomodulatory targets［J］.Nature Reviews Drug Discovery,2015,14(8):561-584.
[28]ZHOU Y,MIAO J,WU H,et al.PD-1 and PD-L1 expression in 132 recurrent nasopharyngeal carcinoma:the correlation with anemia and outcomes［J］.Oncotarget,2017,8(31):51210-51223.
[29]FENG C,ZHANG L,CHANG X,et al.Regulation of post-translational modification of PD-L1 and advances in tumor immunotherapy［J］.Frontiers in Immunology,2023,14:1230135.
[30]ZHANG J,FANG W,QIN T,et al.Co-expression of PD-1 and PD-L1 predicts poor outcome in nasopharyngeal carcinoma［J］.Medical Oncology(Northwood,London,England),2015,32(3):86.
[31]CAO C,WEI Q,TANG X,et al.PD-1 and PD-L1 in locoregionally advanced nasopharyngeal carcinoma:Substudy of a randomized phase III trial［J］.Head & Neck,2019,41(5):1427-1433.
[32]LU J,CHEN XM,HUANG HR,et al.Detailed analysis of inflammatory cell infiltration and the prognostic impact on nasopharyngeal carcinoma［J］.Head & Neck,2018,40(6):1245-1253.
[33]KHAN M,AROOJ S,WANG H.Soluble B7-CD28 family inhibitory immune checkpoint proteins and anti-cancer immunotherapy［J］.Frontiers in Immunology,2021,12:651634.
[34]HU P,LIU Q,DENG G,et al.The prognostic value of cytotoxic T-lymphocyte antigen 4 in cancers:a systematic review and meta-analysis［J］.Scientific Reports,2017,7:42913.
[35]SALVI S,FONTANA V,BOCCARDO S,et al.Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer［J］.Cancer Immunology,Immunotherapy,2012,61(9):1463-1472.
[36]RAFFIN C,VO LT,BLUESTONE JA.T(reg) cell-based therapies:challenges and perspectives［J］.Nature Reviews Immunology,2020,20(3):158-172.
[37]CADENAS-DE MIGUEL S,LUCIANER G,ELIA I.The metabolic cross-talk between cancer and T cells［J］.Trends in Biochemical Sciences,2023,48(7):597-609.
[38]LAI C,AUGUST S,ALBIBAS A,et al.OX40+ regulatory T cells in cutaneous squamous cell carcinoma suppress effector T-cell responses and associate with metastatic potential［J］.Clinical Cancer Research,2016,22(16):4236-4248.
[39]HUANG LQ,WANG JX,HE K,et al.Analysis of peripheral blood T-cell subsets and regulatory T-cells in multiple myeloma patients［J］.Cellular and Molecular Biology(Noisy-le-Grand,France),2018,64(5):113-117.
[40]LIU Y,YUN X,GAO M,et al.Analysis of regulatory T cells frequency in peripheral blood and tumor tissues in papillary thyroid carcinoma with and without Hashimoto's thyroiditis［J］.Clinical & Translational Oncology,2015,17(4):274-280.
[41]WANG J,LUO Y,BI P,et al.Mechanisms of Epstein-Barr virus nuclear antigen 1 favor Tregs accumulation in nasopharyngeal carcinoma［J］.Cancer Medicine,2020,9(15):5598-5608.
[42]SWIECKI M,COLONNA M.The multifaceted biology of plasmacytoid dendritic cells［J］.Nature Reviews Immunology,2015,15(8):471-485.
[43]MORANTE-PALACIOS O,FONDELLI F,BALLESTER E,et al.Tolerogenic dendritic cells in autoimmunity and inflammatory diseases［J］.Trends in Immunology,2021,42(1):59-75.
[44]TREILLEUX I,BLAY JY,BENDRISS-VERMARE N,et al.Dendritic cell infiltration and prognosis of early stage breast cancer［J］.Clinical Cancer Research,2004,10(22):7466-7474.
[45]CHEN YP,YIN JH,LI WF,et al.Single-cell transcriptomics reveals regulators underlying immune cell diversity and immune subtypes associated with prognosis in nasopharyngeal carcinoma［J］.Cell Research,2020,30(11):1024-1042.
[46]LIU Y,HE S,WANG XL,et al.Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution［J］.Nature Communications,2021,12(1):741.

Memo

Memo:
National Natural Science Foundation of China（No.82060556）;国家自然科学基金计划项目（编号：82060556）；贵州省卫生健康委科学技术基金项目（编号：gzwkj2022-020）；贵州省科技计划项目［编号：黔科合成果-LC(2023)029］
Last Update: 2023-11-30