Pancreatic cancer regression by intratumoural injection of live Streptococcus pyogenes in a syngeneic mouse model

Maletzki, C.; Linnebacher, M.; Kreikemeyer, B.; Emmrich, J.
April 2008
Gut;Apr2008, Vol. 57 Issue 4, p483
Academic Journal
Background: This study addressed the potential of bacteriolytic therapy using Streptococcus pyogenes in a syngeneic pancreatic carcinoma mouse model. Methods: PancO2 tumours were either infected with S pyogenes or were treated with the equivalent volume of vehicle. In addition to assessment of tumour histology and immunohistochemistry, isolated splenocytes were analysed by flow cytometry. Interferon (IFN) γ secretion as a reaction of splenocytes against tumour cells was shown through the ELISpot technique. A cytotoxic effect of lymphocytes against tumour targets was detected by lactate dehydrogenase (LDH) release. Cytokine levels in serum were measured. Results: A single application of live bacteria into established PancO2 tumours resulted in complete tumour regression. This antitumoural effect was accompanied by massive leucocyte infiltration into the tumours as well as a significant and sustained elevation of systemic levels of the proinflammatory cytokines IFNγ, tumour necrosis factor α and interleukin 6. Lymphocytes obtained from treated mice specifically recognised syngeneic tumour cells in IFNγ-ELlSpot, and most importantly in cellular cytotoxicity assays, indicating a tumour-specific immune response. Conclusions: We provide data that both the direct lytic activity of S pyogenes towards tumour cells and the infection-driven infiltration of tumours by cells of the innate immune system lead to damage of tumour cells followed by a dissemination of tumour components. This last outcome allows for the activation of tumour-specific effector cells, most probably in draining lymph nodes, promoted by the proinflammatory context. Taken together, these data indicate that the application of live S pyogenes may be a promising new treatment strategy for advanced pancreatic cancer patients that warrants further investigation.


Related Articles

  • The CXC Chemokine MIG/CXCL9 Is Important in Innate Immunity against Streptococcus pyogenes. Egesten, Arne; Eliasson, Mette; Johansson, Helena M.; Olin, Anders I.; Mörgelin, Matthias; Mueller, Anja; Pease, James E.; Frick, Inga-Maria; Björck, Lars // Journal of Infectious Diseases;3/1/2007, Vol. 195 Issue 5, p684 

    Pharyngitis caused by Streptococcus pyogenes is one of the most common bacterial infections in humans and is also a starting point for invasive S. pyogenes infection. Here, we describe that tonsil fluid from patients with streptococcal pharyngitis contains high amounts of the interferon...

  • Synergistic effects of streptolysin S and streptococcal pyrogenic exotoxin B on the mouse model of group A streptococcal infection. Hung, Chih-Hsin; Tsao, Nina; Zeng, Yi-Fang; Lu, Shiou-Ling; Chiang-Ni, Chuan; Lin, Yee-Shin; Wu, Jiunn-Jong; Kuo, Chih-Feng // Medical Microbiology & Immunology;Aug2012, Vol. 201 Issue 3, p357 

    Streptococcus pyogenes is a group A streptococcus (GAS) and an important human pathogen that causes a variety of diseases. Streptococcal pyrogenic exotoxin B (SPE B) and streptolysin S (SLS) are important virulence factors involved in GAS infection, but it is not clear which one is more...

  • Maturation of monocyte derived dendritic cells with OK432 boosts IL-12p70 secretion and conveys strong T-cell responses. Hovden, Arnt-Ove; Karlsen, Marie; Jonsson, Roland; Aarstad, Hans Jørgen; Appel, Silke // BMC Immunology;2011, Vol. 12 Issue 1, p1 

    Background: Design of tumour specific immunotherapies using the patients' own dendritic cells (DC) is a fast advancing scientific field. The functional qualities of the DC generated in vitro are critical, and today's gold standard for maturation is a cytokine cocktail consisting of IL-1b, IL-6,...

  • SPECIFIC CHARACTERISTIC S OF CYTOKINE STATUS IN PATIENTS WITH CHRONICTON SILLITIS OF DIFFEREN TAETIOLOGY. Krasnitskaya, A. S.; Polytika, A. N. // Pacific Medical Journal / Tihookeanskij Medicinskij Zurnal;Jan2013, Vol. 51 Issue 1, p46 

    The authors have examined in dynamic 50 patients (31 women and 19 men) aged 20 to 43 years old with chronic tonsillitis during exacerbation. Twenty patients were diagnosed for Epstein- Barr virus, thirty patients were diagnosed for Streptococcus pyogenes. The interleukin-10 content increased...

  • Intra-tumoral IFN-γ -producing Th22 cells correlate with TNM staging and the worst outcomes in pancreatic cancer. Niccolai, Elena; Taddei, Antonio; Ricci, Federica; Rolla, Simona; D'Elios, Mario Milco; Benagiano, Marisa; Bechi, Paolo; Bencini, Lapo; Ringressi, Maria Novella; Pini, Alessandro; Castiglione, Francesca; Giordano, Daniele; Satolli, Maria Antonietta; Coratti, Andrea; Cianchi, Fabio; Bani, Daniele; Prisco, Domenico; Novelli, Francesco; Amedei, Amedeo // Clinical Science;Feb2016, Vol. 130 Issue 4, p247 

    PDAC (pancreatic ductal adenocarcinoma) is the fifth leading cause of cancer-related death. The causes of this cancer remain unknown, but increasing evidence indicates a key role of the host immune response and cytokines in human carcinogenesis. Intra-tumoral IL (interleukin)-22 levels have been...

  • Protective Effect of Hainosankyuto, a Traditional Japanese Medicine, on Streptococcus pyogenes Infection in Murine Model. Minami, Masaaki; Ichikawa, Mariko; Hata, Nanako; Hasegawa, Tadao // PLoS ONE;2011, Vol. 6 Issue 7, p1 

    Background: Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcal toxic shock syndrome. One serious problem observed recently with S. pyogenes therapy is attenuation of the antibiotic effect, especially penicillin treatment failure...

  • Contribution of Natural Killer Cells to the Pathogenesis of Septic Shock Induced by Streptococcus pyogenes in Mice. Goldmann, Oliver; Chhatwal, Gursharan S.; Medina, Eva // Journal of Infectious Diseases;4/15/2005, Vol. 191 Issue 8, p1280 

    Natural killer (NK) cells are critical components of the innate immune system and have been implicated in the pathogenesis of septic shock. In the present study, the relative contribution of NK cells to the development of Streptococcus pyogenes-induced septic shock was investigated in a mouse...

  • Pancreatic Enzyme Extract Improves Survival in Murine Pancreatic Cancer. Saruc, M.; Standop, S.; Standop, J.; Nozawa, F.; Itami, A.; Pandey, K. K.; Batra, S. K.; Gonzalez, N. J.; Guesry, P.; Pour, P. M. // Nutritional Perspectives: Journal of the Council on Nutrition;Oct2004, Vol. 27 Issue 4, p44 

    Presents a study which examined the effect of porcine pancreatic enzyme (PPE) extracts on human pancreatic cancer (PC) xenografts in nude mice. Transplantation of malignant human PC cell line AsPC1 into the pancreas of male beige XID nude mice; Rate of survival of PPE-treated mice; Affirmation...

  • Type I Interferon Production Induced by Streptococcus pyogenes-Derived Nucleic Acids Is Required for Host Protection. Gratz, Nina; Hartweger, Harald; Matt, Ulrich; Kratochvill, Franz; Janos, Marton; Sigel, Stefanie; Drobits, Barbara; Li, Xiao-Dong; Knapp, Sylvia; Kovarik, Pavel // PLoS Pathogens;May2011, Vol. 7 Issue 5, Special section p1 

    Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes...


Read the Article


Sign out of this library

Other Topics