Regulatory T-cell Density and Cytotoxic T Lymphocyte Density Are Associated with Complete Response to Neoadjuvant Paclitaxel and Carboplatin Chemoradiotherapy in Gastric Cancer

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2018 Oct 23

PMID 30344657

Citations 5

Authors

Di Huang

Yongjiang Yang

Shuai Zhang

Zhuobin Su

Tao Peng

Xiaoyuan Wang

Yifeng Zhao

Shuguang Li

Affiliations

Soon will be listed here.

Abstract

Regulatory T-cell density and cytotoxic T lymphocyte density are crucial in regulating antitumor immune responses. Tumor infiltration has marked therapeutic effects in gastric carcinoma, and there is evidence that chemoradiotherapy (CRT) exhibits an immune-mediated component. In the present study, the density of CD4 and CD8 cells were evaluated in post-CRT surgical samples from 68 patients with gastric cancer using immunohistochemistry. The associations between T-cell density, cytotoxic T lymphocyte density and clinical survival rate were also analyzed. Cytotoxic T lymphocyte density was associated with gastric carcinoma regression grade and regulatory T-cell density was also associated with gastric carcinoma regression grade. Of the patients who had a pathologic complete response, 84 and 76% were found to have a high CD3 and CD4 cell density, which was significantly different to patients who had a low CD3 and CD4 cell density. High cytotoxic T lymphocyte density was also associated with improved survival rates of patients with gastric cancer. In conclusion, these outcomes indicated that regulatory T-cell density and cytotoxic T lymphocyte density in the tumor microenvironment were associated with the response to neoadjuvant CRT and may represent a therapeutic target for gastric cancer.

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References

Petrioli R, Roviello G, Zanotti L, Roviello F, Polom K, Bottini A . Epirubicin-based compared with docetaxel-based chemotherapy for advanced gastric carcinoma: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2016; 102:82-8. DOI: 10.1016/j.critrevonc.2016.04.001. View

Zhu Y, Liu N, Xiong S, Zheng Y, Chu Y . CD4+Foxp3+ regulatory T-cell impairment by paclitaxel is independent of toll-like receptor 4. Scand J Immunol. 2011; 73(4):301-8. DOI: 10.1111/j.1365-3083.2011.02514.x. View

Wang X, Pang L, Feng J . A phase II study of etoposide, doxorubicin, and carboplatin in the treatment of advanced gastric cancer. Am J Clin Oncol. 2002; 25(1):71-5. DOI: 10.1097/00000421-200202000-00015. View

Mobayed M, Heilbrun L, Shields A, Washington T, Venkatramanamoorthy R, Philip P . Safety and Feasibility of Carboplatin and Paclitaxel followed by Fluoropyrimidine Analogs and Radiation as Adjuvant Therapy for Gastric Cancer. Case Rep Oncol. 2010; 2(3):220-228. PMC: 2914386. DOI: 10.1159/000250082. View

van der Sluis F, van Westreenen H, van Etten B, van Leeuwen B, de Bock G . Pretreatment identification of patients likely to have pathologic complete response after neoadjuvant chemoradiotherapy for rectal cancer. Int J Colorectal Dis. 2017; 33(2):149-157. DOI: 10.1007/s00384-017-2939-9. View

Li L, Wen X, Bu Z, Cheng X, Xing X, Wang X . Paclitaxel enhances tumoricidal potential of TRAIL via inhibition of MAPK in resistant gastric cancer cells. Oncol Rep. 2016; 35(5):3009-17. DOI: 10.3892/or.2016.4666. View

Dworak O, Keilholz L, Hoffmann A . Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997; 12(1):19-23. DOI: 10.1007/s003840050072. View

Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T . Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011; 29(6):610-8. DOI: 10.1200/JCO.2010.30.5425. View

Wang X, Li G, Zhang Y, Bai S, Xu F, Wei Y . Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). Med Dosim. 2013; 38(4):395-400. DOI: 10.1016/j.meddos.2013.04.007. View

10.

Chen J, Zhu J, Hong J, Chen M, Lu J, Chen W . Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo. World J Gastroenterol. 2007; 13(4):509-14. PMC: 4065971. DOI: 10.3748/wjg.v13.i4.509. View

11.

Suzuki H, Mori H . World trends for H. pylori eradication therapy and gastric cancer prevention strategy by H. pylori test-and-treat. J Gastroenterol. 2017; 53(3):354-361. PMC: 5847180. DOI: 10.1007/s00535-017-1407-1. View

12.

Haas M, Buttner M, Rau T, Fietkau R, Grabenbauer G, Distel L . Inflammation in gastric adenocarcinoma of the cardia: how do EBV infection, Her2 amplification and cancer progression influence tumor-infiltrating lymphocytes?. Virchows Arch. 2011; 458(4):403-11. DOI: 10.1007/s00428-011-1058-1. View

13.

Koyama S . Differential expression of intracellular apoptotic signaling molecules in tumor and tumor-infiltrating lymphocytes during development of invasion and/or metastasis of gastric carcinoma. Dig Dis Sci. 2004; 48(12):2290-300. DOI: 10.1023/b:ddas.0000007865.96569.9a. View

14.

Kocakova I, Vetcha H, Soumarova R, Vyzula R . [Role of adjuvant chemoradiotherapy in the treatment of gastric carcinoma]. Cas Lek Cesk. 2003; 142 Suppl 1:26-8. View

15.

Bollschweiler E, Berlth F, Baltin C, Monig S, Holscher A . Treatment of early gastric cancer in the Western World. World J Gastroenterol. 2014; 20(19):5672-8. PMC: 4024776. DOI: 10.3748/wjg.v20.i19.5672. View

16.

Yoshikawa T, Aoyama T, Hayashi T, Kuwabara H, Mikayama Y, Ogata T . [Neoadjuvant chemotherapy for gastric cancer--evidence from the world and future strategy in Japan]. Gan To Kagaku Ryoho. 2012; 39(6):866-70. View

17.

Sher D . Neoadjuvant Chemoradiotherapy for Stage III Non-Small Cell Lung Cancer. Front Oncol. 2017; 7:281. PMC: 5722802. DOI: 10.3389/fonc.2017.00281. View

18.

Brandt D, Sergon M, Abraham S, Mabert K, Hedrich C . TCRCD3CD4CD8 effector T cells in psoriasis. Clin Immunol. 2017; 181:51-59. DOI: 10.1016/j.clim.2017.06.002. View

19.

Papadimitriou K, Vassiliou V, Kountourakis P, Polyviou P, Andreopoulos D, Papamichael D . Adjuvant chemoradiotherapy (CRT) for high-risk gastric cancer (GC) patients: single-center experience using infusional 5-fluorouracil (5FU) and radiotherapy (RT). Med Oncol. 2012; 29(4):2716-7. DOI: 10.1007/s12032-012-0206-z. View

20.

Fukuda K, Tsujitani S, Maeta Y, Yamaguchi K, Ikeguchi M, Kaibara N . The expression of RCAS1 and tumor infiltrating lymphocytes in patients with T3 gastric carcinoma. Gastric Cancer. 2002; 5(4):220-7. DOI: 10.1007/s101200200038. View