scholarly journals Reduced tumor growth after low-dose irradiation or immunization against blastic suppressor T cells.

1981 ◽  
Vol 78 (3) ◽  
pp. 1809-1812 ◽  
Author(s):  
A. F. Tilkin ◽  
N. Schaaf-Lafontaine ◽  
A. Van Acker ◽  
M. Boccadoro ◽  
J. Urbain
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Low Dose ◽  
Suppressor T Cells ◽  
Dose Irradiation

scholarly journals Evaluation of Anti-Tumor Effects of Whole-Body Low-Dose Irradiation in Metastatic Mouse Models

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1126
Author(s):  
Kyung-Hee Song ◽  
Seung-Youn Jung ◽  
Jeong-In Park ◽  
Jiyeon Ahn ◽  
Jong-Kuk Park ◽  
...  
Keyword(s):  
T Cells ◽  
Radiation Therapy ◽  
Tumor Growth ◽  
Mouse Models ◽  
Low Dose ◽  
Whole Body ◽  
High Dose ◽  
Mesenchymal Transition ◽  
Dose Irradiation ◽  
Dose Radiation

Low-dose irradiation (LDI) has recently been shown to have various beneficial effects on human health, such as on cellular metabolic activities, DNA repair, antioxidant activity, homeostasis potency, and immune activation. Although studies on the immunogenic effects of LDI are rapidly accumulating, clinical trials for cancer treatment are considered premature owing to the lack of available preclinical results and protocols. Here, we aim to investigate anti-tumor and anti-metastatic effects of whole-body LDI in several tumor-bearing mouse models. Mice were exposed to single or fractionated whole-body LDI prior to tumor transplantation, and tumor growth and metastatic potential were determined, along with analysis of immune cell populations and expression of epithelial–mesenchymal transition (EMT) markers. Whole-body fractionated-LDI decreased tumor development and lung metastasis not only by infiltration of CD4+, CD8+ T-cells, and dendritic cells (DCs) but also by attenuating EMT. Moreover, a combination of whole-body LDI with localized high-dose radiation therapy reduced the non-irradiated abscopal tumor growth and increased infiltration of effector T cells and DCs. Therefore, whole-body LDI in combination with high-dose radiation therapy could be a potential therapeutic strategy for treating cancer.

scholarly journals P04.34 Low-dose irradiation increases recruitment and effector function of tumor-specific T cells in experimental gliomas

2018 ◽  
Vol 20 (suppl_3) ◽  
pp. iii286-iii286
Author(s):  
X Zhang ◽  
K Sahm ◽  
J Sonner ◽  
K Jähne ◽  
M Breckwoldt ◽  
...  
Keyword(s):  
T Cells ◽  
Low Dose ◽  
Effector Function ◽  
Experimental Gliomas ◽  
Dose Irradiation

scholarly journals Regression and inhibition of sarcoma growth by interference with a radiosensitive T-cell population.

1978 ◽  
Vol 148 (3) ◽  
pp. 799-804 ◽  
Author(s):  
K E Hellström ◽  
I Hellström ◽  
J A Kant ◽  
J D Tamerius
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Cell Population ◽  
Whole Body ◽  
Spleen Cells ◽  
Suppressor T Cells ◽  
Irradiation Irradiation

BALB/c mice were inoculated subcutaneously with 10(6) cells from either of two syngeneic sarcomas 1315 and 1425. 6--8 days later, the mice were randomized into groups which were left untreated or given 400 rads of whole body irradiation. Irradiation significantly retarded the growth of both sarcomas, and complete regressions were seen of approximately equal to 30% of the small, established 1315 tumors. The anti-tumor effect of irradiation was abolished if the irradiated mice were inoculated with a T-cell-enriched (but not with a T-cell deprived) suspension of syngeneic spleen cells, suggesting that the irradiation inhibited tumor growth by affecting a radiosensitive population of host suppressor T cells.

scholarly journals Generation and decay of the immune response to a progressive fibrosarcoma. I. Ly-1+2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells.

1984 ◽  
Vol 159 (5) ◽  
pp. 1295-1311 ◽  
Author(s):  
R J North ◽  
I Bursuker
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Effector T Cells ◽  
Suppressor T Cells ◽  
Established Tumor ◽  
Concomitant Immunity ◽  
Progressive Growth ◽  
Adoptive Immunity ◽  
Gamma Irradiated ◽  
Tumor Implant

It was shown that the progressive growth of the immunogenic meth A fibrosarcoma in its semisyngeneic host results in the generation of concomitant immunity to the growth of a tumor implant. The generation of immunity occurred between days 6 and 9 of tumor growth and was associated with the generation of sensitized T cells that were capable, on passive transfer, of causing regression of a 3-d tumor in gamma-irradiated recipients. After day 9 of tumor growth, concomitant immunity and the T cells able to passively transfer it were progressively lost, and this was associated with the generation of splenic suppressor T cells able to suppress the expression of adoptive immunity against an established tumor in T cell-deficient ( TXB ) recipients. The T cells that passively transferred concomitant immunity were shown to be of the Ly-1-2+ phenotype, in contrast to the T cells that transferred suppression, which were shown with the same reagents to be Ly-1+2-. The results are consistent with the hypothesis that the progressive growth of an immunogenic tumor results in the generation of Ly-1-2+-sensitized effector T cells that fail to reach a number sufficient to destroy the tumor because their generation is down-regulated by tumor-induced Ly-1+2- suppressor T cells.

scholarly journals Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma

2020 ◽  
Vol 8 (2) ◽  
pp. e000537
Author(s):  
Hampartsoum B Barsoumian ◽  
Rishab Ramapriyan ◽  
Ahmed I Younes ◽  
Mauricio S Caetano ◽  
Hari Menon ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Low Dose ◽  
Checkpoint Inhibitors ◽  
Macrophage Polarization ◽  
High Dose ◽  
Primary Tumor Site ◽  
Secondary Tumors ◽  
M1 Macrophage

BackgroundDespite some successes with checkpoint inhibitors for treating cancer, most patients remain refractory to treatment, possibly due to the inhibitory nature of the tumor stroma that impedes the function and entry of effector cells. We devised a new technique of combining immunotherapy with radiotherapy (XRT), more specifically low-dose XRT, to overcome the stroma and maximize systemic outcomes.MethodsWe bilaterally established 344SQ lung adenocarcinoma tumors in 129Sv/Ev mice. Primary and secondary tumors were irradiated with either high-dose or low-dose of XRT with systemic anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte associated protein 4 administration. Survival and tumor growth were monitored for the various groups, and secondary tumors were phenotyped by flow cytometry for immune populations. Tumor growth factor-beta (TGF-β) cytokine levels were assessed locally after low-dose XRT, and specific immune-cell depletion experiments were conducted to identify the major contributors to the observed systemic antitumor effect.ResultsThrough our preclinical and clinical studies, we observed that when tumor burden was high, there was a necessity of combining high-dose XRT to ‘prime’ T cells at the primary tumor site, with low-dose XRT directed to secondary (metastatic) tumors to ‘modulate the stroma’. Low-dose XRT improved the antitumor outcomes of checkpoint inhibitors by favoring M1 macrophage polarization, enhancing natural killer (NK) cell infiltration, and reducing TGF-β levels. Depletion of CD4+ T cells and NK cells abrogated the observed antitumor effect.ConclusionOur data extend the benefits of low-dose XRT to reprogram the tumor environment and improve the infiltration and function of effector immune cells into secondary tumors.

scholarly journals Radiation-induced, immunologically mediated regression of an established tumor as an example of successful therapeutic immunomanipulation. Preferential elimination of suppressor T cells allows sustained production of effector T cells.

1986 ◽  
Vol 164 (5) ◽  
pp. 1652-1666 ◽  
Author(s):  
R J North
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Tumor Regression ◽  
Effector T Cells ◽  
Whole Body ◽  
Suppressor T Cells ◽  
Established Tumor ◽  
Published Evidence ◽  
The One ◽  
Immunocompetent Mice

The results of this study confirm results published by others by showing that sublethal whole-body irradiation of mice bearing immunogenic tumors can result in complete tumor regression. The results show, in addition, that irradiation-induced tumor regression can be prevented by infusion, after irradiation, of Ly-1+,2-,L3T4+ suppressor T cells from the spleens of donors bearing an established tumor, but not by infusion of normal spleen cells. This evidence, plus the demonstration that irradiation fails to cause regression of tumors growing in immunocompetent mice, is consistent with the hypothesis that irradiation-induced regression is immunologically mediated, and that it depends on the ability of irradiation to preferentially eliminate suppressor T cells. By using passive transfer assays to measure the production of effector T cells and suppressor T cells against time of tumor growth, it was shown that irradiation of tumor-bearing mice on day 5 of tumor growth resulted in a failure to generate suppressor T cells on the one hand, and in a sustained production, effector T cells on the other. In other words, irradiation prevented the concomitant antitumor immune response from being downregulated by suppressor T cells. However, giving radiation on day 1 of tumor growth, in contrast to giving it 3-6 d later, caused immunodepression and enhancement of tumor growth. This is in keeping with published evidence showing that, whereas resting effector T cells are highly radiosensitive, antigen-activated effector T cells are relatively radioresistant. It is suggested that the radioresistance of activated effector T cells, coupled with the radiosensitivity of activated suppressor T cells, is the reason for the selectivity of ionizing radiation for suppressor T cells and why a tumor needs to be palpable to undergo regression in response to radiation therapy.

THE ROLE OF SUPPRESSOR T CELLS IN THE DEVELOPMENT OF LOW-DOSE PARALYSIS TO TYPE III PNEUMOCOCCAL POLYSACCARIDE

1974 ◽  
pp. 493-502 ◽  
Author(s):  
Phillip J. Baker ◽  
William H. Burns ◽  
Benjamin Prescott ◽  
Philip W. Stashak ◽  
Diana F. Amsbaugh
Keyword(s):  
T Cells ◽  
Low Dose ◽  
Suppressor T Cells ◽  
Type Iii

Susceptibility to Theiler’s murine encephalomyelitis virus-induced demyelinating disease in BALB/cAnNCr mice is related to absence of a CD4+ T-cell subset

2002 ◽  
Vol 8 (6) ◽  
pp. 469-474 ◽  
Author(s):  
K A Karls ◽  
P W Denton ◽  
R W Melvold
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Low Dose ◽  
Demyelinating Disease ◽  
Cell Subset ◽  
T Cell Subset ◽  
Theiler’S Murine Encephalomyelitis Virus ◽  
Dose Irradiation ◽  
Encephalomyelitis Virus

Two histocompatible substrains of BALB/c mice (BALB/cByJ, BALB/cAnNCr) are resistant and susceptible, respectively, to Theiler’s murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) - a model for viral etiology of human multiple sclerosis. BALB/cByJ mice become susceptible following low-dose irradiation given prior to infection. Resistance is restored by adoptive transfer of CD8+ (but not CD4+) splenic T cells from infected, unirradiated BALB/cByJ donors. In contrast, resistance is conferred to BALB/cAnNCr mice by adoptive transfer of either CD4+ or CD8+ T cells from resistant BALB/cByJ donors. T cells from BALB/cAnNCr mice cannot confer protection. To integrate these two observations, we hypothesized that the BALB/cAnNCr mice possess precursors of the regulatory CD8+ T cells, but fail to activate them because they lack a critical CD4+ T-cell subpopulation. We tested this model using serial transfers. The transfer of CD4+ T cells from the BALB/cByJ to the BALB/cAnNCr mice permitted development of BALB/cAnNCr CD8+ T cells that, in turn, provided resistance when transferred into susceptible recipients. The BALB/cByJ CD4+ T cells, which activated the CD8+ cells, were sensitive to low-dose irradiation, unlike CD4+ T cells involved in the later inflammatory demyelination. Thus, susceptibility of BALB/cAnNCr mice is due to a defective/absent CD4+ T -cell subset acting immediately after infection.

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