The Tumor Growth-Promoting Effect of Allogeneic Blood Transfusions

1995 ◽  
Vol 24 (1-2) ◽  
pp. 311-317 ◽  
Author(s):  
M. A. Blajchman ◽  
J. O. Bordin
Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1880-1882
Author(s):  
MA Blajchman ◽  
L Bardossy ◽  
R Carmen ◽  
A Sastry ◽  
DP Singal

Allogeneic blood transfusions have been reported to induce immunomodulation in recipients of blood products. While the mechanism(s) of this immunomodulatory effect is unknown, it has been suggested that this effect of allogeneic blood transfusions could adversely affect patients with a malignant disorder. These concerns have been supported by a number of nonrandomized, mainly retrospective, clinical studies which indicate that allogeneic blood transfusions can adversely affect prognosis following the surgical treatment of oncology patients. Recently, we have shown that allogeneic blood transfusions enhance primary tumor growth and increase metastatic pulmonary nodule formation in inbred mice. The tumor growth-promoting activity of allogeneic blood transfusions was studied also using outbred rabbits. In this present study, we demonstrate that the tumor growth-promoting effect of allogeneic blood transfusions is mediated by donor leukocytes and that this effect can be abolished by their removal before transfusion. We show also that the allogeneic blood transfusion tumor growth-promoting effect can be passively transferred to naive animals (both mice and rabbits) using spleen cells from allogeneically transfused animals. In these experiments, numbers of metastatic pulmonary nodules were significantly increased in both mice and rabbits that had received spleen cells from allogeneically transfused animals compared with those that had received spleen cells from syngeneically transfused animals, or from animals that had been transfused with leukodepleted allogeneic blood.


Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1880-1882 ◽  
Author(s):  
MA Blajchman ◽  
L Bardossy ◽  
R Carmen ◽  
A Sastry ◽  
DP Singal

Abstract Allogeneic blood transfusions have been reported to induce immunomodulation in recipients of blood products. While the mechanism(s) of this immunomodulatory effect is unknown, it has been suggested that this effect of allogeneic blood transfusions could adversely affect patients with a malignant disorder. These concerns have been supported by a number of nonrandomized, mainly retrospective, clinical studies which indicate that allogeneic blood transfusions can adversely affect prognosis following the surgical treatment of oncology patients. Recently, we have shown that allogeneic blood transfusions enhance primary tumor growth and increase metastatic pulmonary nodule formation in inbred mice. The tumor growth-promoting activity of allogeneic blood transfusions was studied also using outbred rabbits. In this present study, we demonstrate that the tumor growth-promoting effect of allogeneic blood transfusions is mediated by donor leukocytes and that this effect can be abolished by their removal before transfusion. We show also that the allogeneic blood transfusion tumor growth-promoting effect can be passively transferred to naive animals (both mice and rabbits) using spleen cells from allogeneically transfused animals. In these experiments, numbers of metastatic pulmonary nodules were significantly increased in both mice and rabbits that had received spleen cells from allogeneically transfused animals compared with those that had received spleen cells from syngeneically transfused animals, or from animals that had been transfused with leukodepleted allogeneic blood.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 831-831
Author(s):  
Morris A. Blajchman ◽  
Reginald M. Gorczynski ◽  
David A. Clark

Abstract Background: The transfusion of blood products containing allogeneic leukocytes can alter recipient resistance to infection and stimulate the growth of some types of tumors in animal models of transfusion-induced tumor growth. Transfusion related immunomodulation (TRIM) represents a credible mechanism for the altered resistance to infection seen clinically, but cannot explain the growth of non-immunogenic tumors in syngeneic hosts seen regularly in the various transfusion-related animal models of tumor growth. Methods and Results: In this study the transfusion of 50–200 μL of unmodified anticoagulated allogeneic BALB/c (H-2d) mouse blood into C57B1/6 (H-2b) mice, four days before being intravenously injected with syngeneic (H-2b) FSL10 fibrosarcoma cells (1–2 x 106 cells per mouse) resulted in a significant increase in the number of pulmonary nodules observed at 3 weeks compared to that seen in control mice. The median number of pulmonary nodules increased in an allogeneic blood transfusion dose-dependent manner, as did the proportion of mice without pulmonary nodules. This tumor growth-promoting effect of the allogeneic blood transfusions required the presence in the transfused blood of allogeneic CD11c+ dendritic cells bearing the CD200 co-stimulatory tolerance signal. This tumor growth-promoting effect of allogeneic blood could be blocked by specific monoclonal antibodies to either CD11c or to CD200. CD200 receptor-mediated signaling alone, in the absence of alloantigen, failed to augment the number of TRIM-induced pulmonary tumor nodules. Physiological concentrations of TGFβ, but not IL-10, were shown to stimulate proliferation of FSL10 cells in vitro in these studies. In this context, it is known that CD200 together with alloantigens are known to stimulate development of suppressor cells acting via IL-10 and TGFβ in vivo. Allogeneic blood also caused a significant CD200-dependent accumulation of TGFβ+ suppressor cells in the spleen, 12 days after transfusion, when the spleen cells could be shown to adoptively transfer the TRIM effect to naive animals. Conclusions: These data support the hypothesis that allogeneic transfusions in an allogeneic blood transfusion mouse tumor model results in tumor growth promotion in recipient mice. This effect appears to result in both the induction of TGFβ-producing suppressor cells as well as requiring the transfusion of allogeneic CD11c+ dendritic cells, bearing both CD200 tolerance signaling molecules and alloantigens.


1989 ◽  
Vol 7 (4) ◽  
pp. 333-338
Author(s):  
Masahiko Fujii ◽  
Norio Takahashi ◽  
Takayoshi Fujii ◽  
Haruhisa Hayashi ◽  
Kenichi Matsunaga ◽  
...  

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 344-348 ◽  
Author(s):  
JO Bordin ◽  
L Bardossy ◽  
MA Blajchman

Abstract We had reported previously (Blood 81:1880, 1993) that allogeneic blood transfusions (ABT) administered before the infusion of tumor cells in both inbred and outbred experimental animals promote tumor growth and that this effect can be ameliorated by leukodepletion. To better reproduce the human situation, we evaluated, in this present study, the effect of ABT in animals with established tumors using enumeration of pulmonary metastatic nodules as the end point. The role of allogeneic blood component transfusions in promoting tumor growth and the relative efficacy of prestorage versus poststorage leukodepletion of the ABT in preventing tumor growth enhancement were also evaluated. In an inbred murine animal model, C57Bl/6J mice were administered nonleukodepleted allogeneic (ABT), leukodepleted allogeneic (LD-ABT), or syngeneic (SBT) blood transfusions after the intravenous infusion of syngeneic methylcholanthrene-induced fibrosarcoma cells using two different protocols. A significant increase in the number of pulmonary nodules was observed in those mice that received ABT, in both protocols, compared to animals transfused with SBT or LD-ABT. Significantly higher numbers of pulmonary nodules were also seen in mice transfused with allogeneic buffy-coat leukocytes compared with mice that received either nonleukodepleted allogeneic plasma or LD-ABT. In an outbred animal (rabbit) model, recipient rabbits were administered either nonleukodepleted ABT, prestorage LD-ABT, poststorage LD-ABT, or SBT on days +4 and +9 after the infusion of syngeneic epithelial tumor cells. A significant increase in the number of pulmonary nodules was seen in rabbits that received nonleukodepleted ABT compared to animals transfused with SBT. Significantly lower numbers of pulmonary nodules were observed in rabbits that received prestorage LD-ABT compared to animals transfused with poststorage LD-ABT, but no significant difference was seen in rabbits that received poststorage LD-ABT compared with animals transfused with nonleukodepleted ABT. These studies show that ABT promote tumor growth of established animal tumors, that the ABT-induced tumor growth effect is related to the presence of donor allogeneic leukocytes, and that this effect can be ameliorated by prestorage leukodepletion. The present results also provide evidence for the lack of efficacy of poststorage leukodepletion in preventing ABT tumor growth promotion.(ABSTRACT TRUNCATED AT 400 WORDS).


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
André Luis Lacerda Bachi ◽  
Lívia Caires dos Santos ◽  
Suely Nonogaki ◽  
Sônia Jancar ◽  
Miriam Galvonas Jasiulionis

There is evidence that the platelet-activating factor receptor (PAFR) is involved in the clearance of apoptotic cells by macrophages, and that this is associated with anti-inflammatory phenotype. Our group has previously shown that coinjection of a large number of apoptotic cells can promote tumor growth from a subtumorigenic dose of melanoma cells. Here, we studied the involvement of the PAFR in the tumor growth promoting effect of apoptotic cells. A sub-tumorigenic dose of melanoma cells (Tm1) was coinjected with apoptotic Tm1 cells, subcutaneously in the flank of C57Bl/6 mice, and the volume was monitored for 30 days. Animals received the PAFR antagonists, WEB2170 or PCA4248 (5 mg/kg body weight) or vehicle, by peritumoral daily injection for 5 days. Results showed that PAFR antagonists significantly inhibited the tumor growth induced by the coinjection of a sub-tumorigenic dose of melanoma cells together with apoptotic cells. This was accompanied by inhibition of early neutrophil and macrophage infiltration. Addition of (platelet-activating factor) to this system has no significant effect. PAFR antagonists did not affect the promoting effect of carrageenan. We suggest that the recognition of apoptotic cells by phagocytes leads to activation of PAFR pathways, resulting in a microenvironment response favorable to melanoma growth.


2009 ◽  
Vol 278 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Sascha Keller ◽  
Anne-Kathleen König ◽  
Frederik Marmé ◽  
Steffen Runz ◽  
Silke Wolterink ◽  
...  

Blood ◽  
1994 ◽  
Vol 84 (1) ◽  
pp. 344-348
Author(s):  
JO Bordin ◽  
L Bardossy ◽  
MA Blajchman

We had reported previously (Blood 81:1880, 1993) that allogeneic blood transfusions (ABT) administered before the infusion of tumor cells in both inbred and outbred experimental animals promote tumor growth and that this effect can be ameliorated by leukodepletion. To better reproduce the human situation, we evaluated, in this present study, the effect of ABT in animals with established tumors using enumeration of pulmonary metastatic nodules as the end point. The role of allogeneic blood component transfusions in promoting tumor growth and the relative efficacy of prestorage versus poststorage leukodepletion of the ABT in preventing tumor growth enhancement were also evaluated. In an inbred murine animal model, C57Bl/6J mice were administered nonleukodepleted allogeneic (ABT), leukodepleted allogeneic (LD-ABT), or syngeneic (SBT) blood transfusions after the intravenous infusion of syngeneic methylcholanthrene-induced fibrosarcoma cells using two different protocols. A significant increase in the number of pulmonary nodules was observed in those mice that received ABT, in both protocols, compared to animals transfused with SBT or LD-ABT. Significantly higher numbers of pulmonary nodules were also seen in mice transfused with allogeneic buffy-coat leukocytes compared with mice that received either nonleukodepleted allogeneic plasma or LD-ABT. In an outbred animal (rabbit) model, recipient rabbits were administered either nonleukodepleted ABT, prestorage LD-ABT, poststorage LD-ABT, or SBT on days +4 and +9 after the infusion of syngeneic epithelial tumor cells. A significant increase in the number of pulmonary nodules was seen in rabbits that received nonleukodepleted ABT compared to animals transfused with SBT. Significantly lower numbers of pulmonary nodules were observed in rabbits that received prestorage LD-ABT compared to animals transfused with poststorage LD-ABT, but no significant difference was seen in rabbits that received poststorage LD-ABT compared with animals transfused with nonleukodepleted ABT. These studies show that ABT promote tumor growth of established animal tumors, that the ABT-induced tumor growth effect is related to the presence of donor allogeneic leukocytes, and that this effect can be ameliorated by prestorage leukodepletion. The present results also provide evidence for the lack of efficacy of poststorage leukodepletion in preventing ABT tumor growth promotion.(ABSTRACT TRUNCATED AT 400 WORDS).


1990 ◽  
Vol 80 (1) ◽  
pp. 109-113 ◽  
Author(s):  
Ester P. Lorences ◽  
Gordon J. McDougall ◽  
Stephen C. Fry

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