Immune reconstitution from peripheral blood mononuclear cells inhibits lung carcinoma growth in NOD/SCID mice

Liu, Xiang; Li, Huiling; Liu, Jun; Guan, Yubao; Huang, Liyan; Tang, Hailing; He, Jianxing

doi:10.3892/ol.2014.2379

Cited by 6 publications

(13 citation statements)

References 33 publications

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“…These factors, as well as the immunodeficiency status of the PDX models, may contribute to the higher CTC/DTC detection rates we find in PDX models. In future, it will be of interest to compare CTCs/DTCs from patients side-by-side with those derived from matched PDXs as well as to compare characteristics of CTCs/DTCs within various immunodeficiency models and versus those with reconstituted immune components [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis

et al. 2015

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IntroductionReal-time monitoring of biologic changes in tumors may be possible by investigating the transitional cells such as circulating tumor cells (CTCs) and disseminated tumor cells in bone marrow (BM-DTCs). However, the small numbers of CTCs and the limited access to bone marrow aspirates in cancer patients pose major hurdles. The goal of this study was to determine whether breast cancer (BC) patient-derived xenograft (PDX) mice could provide a constant and renewable source of CTCs and BM-DTCs, thereby representing a unique system for the study of metastatic processes.MethodsCTCs and BM-DTCs, isolated from BC PDX-bearing mice, were identified by immunostaining for human pan-cytokeratin and nuclear counterstaining of red blood cell-lysed blood and bone marrow fractions, respectively. The rate of lung metastases (LM) was previously reported in these lines. Associations between the presence of CTCs, BM-DTCs, and LM were assessed by the Fisher’s Exact and Cochran-Mantel-Haenszel tests. Two separate genetic signatures associated with the presence of CTC clusters and with lung metastatic potential were computed by using the expression arrays of primary tumors from different PDX lines and subsequently overlapped to identify common genes.ResultsIn total, 18 BC PDX lines were evaluated. CTCs and BM-DTCs, present as either single cells or clusters, were detected in 83% (15 of 18) and 62.5% (10 to16) of the lines, respectively. A positive association was noted between the presence of CTCs and BM-DTCs within the same mice. LM was previously found in 9 of 18 (50%) lines, of which all nine had detectable CTCs. The presence of LM was strongly associated with the detection of CTC clusters but not with individual cells or detection of BM-DTCs. Overlapping of the two genetic signatures of the primary PDX tumors associated with the presence of CTC clusters and with lung metastatic potential identified four genes (HLA-DP1A, GJA1, PEG3, and XIST). This four-gene profile predicted distant metastases-free survival in publicly available datasets of early BC patients.ConclusionThis study suggests that CTCs and BM-DTCs detected in BC PDX-bearing mice may represent a valuable and unique preclinical model for investigating the role of these rare cells in tumor metastases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0508-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis

et al. 2015

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“…to bladder cancer. However, similar to some of the related studies [6,[14][15][16], this study did not include any T cell functions comparison between the humanized control group and the model group. Yet, we strongly believe that it would be of great significance to our future studies to explore the possibility of interaction between the immune system and the tumors using this model.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

“…Sabzevari H et al [43] demonstrated that when engrafted with T lymphocytes, SCID mice bearing tumors showed a significant reduction of metastasis in the number of foci and in the lymph nodes. Liu et al [6] found the xenograft growth in SCID mice was significantly inhibited by intraperitoneal injection of PBMCs. So they concluded that "PBMC transplantation inhibits lung carcinoma progression via the reconstitution of the immune system, particularly of cytotoxic T lymphocytes.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

Gong

et al. 2015

Cell Physiol Biochem

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Background/Aims: The aim of this study was to develop a novel model by transplanting human bladder cancer xenografts into humanized immunodeficient mice (SCID). Methods: The animals first underwent sublethal irradiation and then were subjected to simultaneous transplantation of human lymphocytes (5 × 10⁷ cells/mouse i.p.) and human bladder cancer cells (3 × 10⁶ cells/mouse s.c.). Results: The xenografts developed in all 12 mice that had received bladder cancer BIU-87 cells, and the tumor specimens were evaluated histologically. All 6 model mice expressed human CD3 mRNA and/or protein in the peripheral blood, spleens and xenografts. The mean proportion of human CD3⁺ cells was 19% with a level of human IgG 532.4µ/ml in the peripheral blood at Week 6 after transplant inoculation. The re-constructed human immune system in these mice was confirmed to be functional by individual in vitro testing of their proliferative, secretory and cytotoxic responses. Conclusion: The successful engraftment of the human bladder cancer xenografts and the establishment of the human immune system in our in vivo model described here may provide a useful tool for the development of novel therapeutic strategies targeting at bladder cancer.

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“…Previous studies have demonstrated that reconstitution of the immune system by transplanting human PBMC hampers tumor growth in immunocompromised mice [27,28]. In this study, tumor volume was measured every alternate day, from day 4 after tumor inoculation.…”

Section: Taso Administration Accelerates Tumor Rejection In Hupbl Nsg Micementioning

confidence: 97%

Targeting transforming growth factor-β2 by antisense oligodeoxynucleotide accelerates T cell-mediated tumor rejection in a humanized mouse model of triple-negative breast cancer

Lee

Shin

et al. 2021

Preprint

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Background: Transforming growth factor (TGF-β) pathway mediates suppression of anti-tumor immunity, and is associated with poor prognosis in triple-negative breast cancer (TNBC). Methods: In this study, we generated a humanized animal model by transplanting human peripheral blood mononuclear cells into immunodeficient mice followed by inoculation of MDA-MB-231 cells, and subsequently analyzed the role of TGF-β2 in the interaction between human T cells and human tumor cells. Results: Following reconstitution of the human immune system, inhibition of TGF-β signaling by TGF-β2 antisense oligodeoxynucleotide (TASO) resulted in accelerated tumor growth inhibition. TGF-β2 inhibition also resulted in downregulation of peripheral Foxp3+ regulatory T cells (Treg), whereas no effect was seen in the expression of CD8+ cytotoxic T cells. Analysis of the TASO-treated mice serum revealed elevated levels of human IFN-γ and reduced levels of human IL-10 and TGF-β2. Moreover, TGF-β2 inhibition resulted in increased CD8+ T cell infiltration, whereas the reduced infiltration of Tregs into the tumor partly resulted from decreased expression of CCL22. Decreased intra-tumoral Tregs facilitated the activation of cytotoxic T cells, associated with increased granzyme B expression. Conclusion: These results indicate that TASO potentiated T-cell mediated antitumor immunity, and it is proposed that TGF-β2 may be a promising target in the immunotherapeutic strategy of TNBC.

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Immune reconstitution from peripheral blood mononuclear cells inhibits lung carcinoma growth in NOD/SCID mice

Cited by 6 publications

References 33 publications

Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis

Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis

Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

Targeting transforming growth factor-β2 by antisense oligodeoxynucleotide accelerates T cell-mediated tumor rejection in a humanized mouse model of triple-negative breast cancer

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