In the entire process, macrophages played an indispensible role in augmenting T-cell aided immunity against established and solid pancreatic tumors.

Holding out potential for effective cancer therapy in future, researchers from German Cancer Research Centre and the University of Hyderabad have found a novel anti-tumor role of low dose of gamma radiation in mice as well as human subjects of pancreatic cancer.

In the study, the researchers irradiated pancreatic tumors bearing mice to low dose of gamma radiation (2Gy) which is around 20 times less than the dose normally used clinically for cancer treatment. The lower dose irradiation significantly triggered T cell immune responses and reduced tumor growth, they found. In a human clinical study, patients in advanced stage of pancreatic cancer were irradiated locally with 2Gy dose of gamma radiation in a therapeutic setting and it produced similar results.

In the entire process, macrophages played an indispensible role in augmenting T-cell aided immunity against established and solid pancreatic tumors.

Macrophages are the integral part of both innate and adaptive immune system and normally involved in destroying invading foreign bodies. Most interestingly, they act like double-edge swords of immune system and could control as well promote tumor growth, mentioned Dr. Hridayesh Prakash, (Ramanujan Fellow), Department of Biochemistry, University of Hyderabad.,

During initial stages of tumor development, these macrophages posses tumour regulatory potential, mediated by nitric oxide and pro-inflammatory factors. However, under the influence of immunosuppressive tumour micro-milieu, they get converted and promote tumor growth.

In further experiments, the researchers found that replacement of resident macrophages with gamma ray programmed macrophages in an adoptive transfer setting was sufficient to augment T cell immunotherapy and successful tumor rejection even in the absence of additional irradiation of recipient tumor bearing mice.

The researchers also found that blocking INOS enzyme activity, the key marker of tumor regulatory macrophages, led to abolishment of T-cell immunotherapy and tumor rejection.

Dr. Prakash said the study demonstrated the role of iNOS+ macrophages in conditioning tumor microenvironment favoring T cell immunotherapy as well as angiogenesis in mice and successful tumor rejection.

He said their novel findings have tremendous therapeutic potential in dealing with persistent bacterial infections like H pylori which is associated with cancer development. The re-activation of macrophages was of paramount requirement for both, effective eradication of pathogens and in minimizing the risk of infections that could lead to cancer.

The work was published in November 2013 in the Cancer Cell journal.

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