Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging

Du,Xiaohui; Wang,Xiangyu; Ning,Ning; Xia,Shaoyou; Liu,Juchao; Liang,Wentao; Sun,Huiwei; Xu,Yingxin

doi:10.3892/etm.2012.579

Dynamic tracing of immune cells in an orthotopic gastric carcinoma mouse model using near-infrared fluorescence live imaging

Authors:
- Xiaohui Du
- Xiangyu Wang
- Ning Ning
- Shaoyou Xia
- Juchao Liu
- Wentao Liang
- Huiwei Sun
- Yingxin Xu
View Affiliations

Affiliations: General Surgery Department, Chinese PLA General Hospital, Beijing, P.R. China, Institute of General Surgery, Chinese PLA General Hospital, Beijing, P.R. China
Published online on: May 17, 2012 https://doi.org/10.3892/etm.2012.579
Pages: 221-225

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Adoptive cellular immunotherapy (ACI) has been demonstrated to be a promising cancer therapeutic, however, the distribution of immune cells injected into a tumor-bearing body is unclear. In this study, we investigated the tumor‑targeting capacity of cytokine-induced killer (CIK) cells and cytotoxic T lymphocytes (CTLs) in a human gastric carcinoma orthotopic mouse model using a near-infrared fluorescence imaging system. CIK cells and tumor-specific CTLs were prepared with the near-infrared fluorescent dye DiR. As expected, no significant change in the proliferation rate or antitumor activity of CIK cells and CTLs was noted after labeling with DiR. Furthermore, a gastric carcinoma orthotopic model was established using a fibrinogen-thrombin method in nude mice followed by intraperitoneal infusion of the labeled immune cells into nude mice with established gastric carcinoma. Dynamic tracing of the immune cells was performed using a fluorescence-based live imaging system. Concentrated fluorescence signals were observed for a minimum of two weeks at the tumor site in mice infused with either CIK cells or CTLs with a peak signal at 48 h. Notably, CTLs were more persistent at the tumor site and exhibited a more intense antitumor activity than CIK cells following infusion. These results provided visual evidence of the tumor-targeting capacity of immune cells in live animals.

View Figures

View References

1.	Rosenberg SA, Yang JC and Restifo NP: Cancer immunotherapy: moving beyond current vaccines. Nat Med. 10:909–915. 2004. View Article : Google Scholar : PubMed/NCBI
2.	Dudley ME, Wunderlich JR, Robbins PF, et al: Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 298:850–854. 2002. View Article : Google Scholar : PubMed/NCBI
3.	Dudley ME, Wunderlich JR, Yang JC, et al: Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory meta-static melanoma. J Clin Oncol. 23:2346–2357. 2005. View Article : Google Scholar : PubMed/NCBI
4.	Frangioni JV: In vivo near-infrared fluorescence imaging. Curr Opin Chem Biol. 7:626–634. 2003. View Article : Google Scholar : PubMed/NCBI
5.	He X, Gao J, Gambhir SS and Cheng Z: Near-infrared fluorescent nanoprobes for cancer molecular imaging: status and challenges. Trends Mol Med. 16:574–583. 2010. View Article : Google Scholar : PubMed/NCBI
6.	Kalchenko V, Shivtiel S, Malina V, et al: Use of lipophilic near-infrared dye in whole-body optical imaging of hematopoietic cell homing. J Biomed Opt. 11:0505072006. View Article : Google Scholar : PubMed/NCBI
7.	Granot D, Addadi Y, Kalchenko V, Harmelin A, Kunz-Schughart LA and Neeman M: In vivo imaging of the systemic recruitment of fibroblasts to the angiogenic rim of ovarian carcinoma tumors. Cancer Res. 67:9180–9189. 2007. View Article : Google Scholar : PubMed/NCBI
8.	Hemmrich K, Meersch M, von Heimburg D and Pallua N: Applicability of the dyes CFSE, CM-DiI and PKH26 for tracking of human preadipocytes to evaluate adipose tissue engineering. Cells Tissues Organs. 184:117–127. 2006. View Article : Google Scholar : PubMed/NCBI
9.	Kikkawa YS and Pawlowski KS: Cochlear neuronal tracing for frequency mapping with DiI, NeuroVue, and Golgi methods. Acta Otolaryngol Suppl. 559:19–23. 2007. View Article : Google Scholar : PubMed/NCBI
10.	Jiang J, Xu N, Wu C, et al: Treatment of advanced gastric cancer by chemotherapy combined with autologous cytokine-induced killer cells. Anticancer Res. 26:2237–2242. 2006.PubMed/NCBI
11.	Kim HM, Kang JS, Lim J, et al: Antitumor activity of cytokine-induced killer cells in nude mouse xenograft model. Arch Pharm Res. 32:781–787. 2009. View Article : Google Scholar
12.	Toh U, Fujii T, Mishima M, et al: Conventional chemotherapy combined with the repetitive immune cell transfer for patients with refractory advanced gastric cancer. Gan To Kagaku Ryoho. 34:1931–1933. 2007.(In Japanese).
13.	Wongkajornsilp A, Sangsuriyong S, Hongeng S, Waikakul S, Asavamongkolkul A and Huabprasert S: Effective osteosarcoma cytolysis using cytokine-induced killer cells pre-inoculated with tumor RNA-pulsed dendritic cells. J Orthop Res. 23:1460–1466. 2005. View Article : Google Scholar : PubMed/NCBI
14.	Yamagishi H, Ueda Y and Oka T: A case report of immunotherapy on a patient with advanced gastric cancer by adoptive transfer of OK-432-reactive HLA-matched allogeneic lymphocytes. Cancer Immunol Immunother. 46:113–119. 1998. View Article : Google Scholar : PubMed/NCBI
15.	Schmidt-Wolf IG, Lefterova P, Johnston V, Huhn D, Blume KG and Negrin RS: Propagation of large numbers of T cells with natural killer cell markers. Br J Haematol. 87:453–458. 1994. View Article : Google Scholar : PubMed/NCBI
16.	Linn YC and Hui KM: Cytokine-induced NK-like T cells: from bench to bedside. J Biomed Biotechnol. 2010:4357452010.PubMed/NCBI
17.	Linn YC, Lau LC and Hui KM: Generation of cytokine-induced killer cells from leukaemic samples with in vitro cytotoxicity against autologous and allogeneic leukaemic blasts. Br J Haematol. 116:78–86. 2002. View Article : Google Scholar : PubMed/NCBI
18.	Lopez RD, Waller EK, Lu PH and Negrin RS: CD58/LFA-3 and IL-12 provided by activated monocytes are critical in the in vitro expansion of CD56⁺ T cells. Cancer Immunol Immunother. 49:629–640. 2001. View Article : Google Scholar : PubMed/NCBI
19.	Mehta BA, Schmidt-Wolf IG, Weissman IL and Negrin RS: Two pathways of exocytosis of cytoplasmic granule contents and target cell killing by cytokine-induced CD3⁺ CD56⁺ killer cells. Blood. 86:3493–3499. 1995.PubMed/NCBI
20.	Koya RC, Mok S, Comin-Anduix B, et al: Kinetic phases of distribution and tumor targeting by T cell receptor engineered lymphocytes inducing robust antitumor responses. Proc Natl Acad Sci USA. 107:14286–14291. 2010. View Article : Google Scholar : PubMed/NCBI
21.	Shu CJ, Radu CG, Shelly SM, et al: Quantitative PET reporter gene imaging of CD8⁺ T cells specific for a melanoma-expressed self-antigen. Int Immunol. 21:155–165. 2009. View Article : Google Scholar : PubMed/NCBI
22.	Butler MO, Lee JS, Ansen S, et al: Long-lived antitumor CD8⁺ lymphocytes for adoptive therapy generated using an artificial antigen-presenting cell. Clin Cancer Res. 13:1857–1867. 2007.PubMed/NCBI
23.	Mackensen A, Meidenbauer N, Vogl S, Laumer M, Berger J and Andreesen R: Phase I study of adoptive T-cell therapy using antigen-specific CD8⁺ T cells for the treatment of patients with metastatic melanoma. J Clin Oncol. 24:5060–5069. 2006. View Article : Google Scholar : PubMed/NCBI
24.	Yamaguchi Y, Ohshita A, Hironaka K, et al: Adoptive immuno-therapy using autologous lymphocytes sensitized with HLA class I-matched allogeneic tumor cells. Oncol Rep. 16:165–169. 2006.PubMed/NCBI
25.	Yee C, Thompson JA, Byrd D, et al: Adoptive T cell therapy using antigen-specific CD8⁺ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA. 99:16168–16173. 2002.PubMed/NCBI