Blood samples

A step forward towards developing immunotherapy for hematological cancers

Tuesday 10 Nov 20

Contact

Sunil Kumar Saini
Assistant Professor
DTU Health Tech
+45 35 88 68 07

Contact

Sine Reker Hadrup
Head of Sections, Professor
DTU Health Tech
+45 35 88 62 90

Collaborators and funding

The work is based on collaboration between researchers from DTU, Rigshospitalet and Herlev Hospital, Copenhagen University Hospital, Denmark, and, Lowy Cancer Research Centre, UNSW, Sydney.

It was funded by grants the European Research Council, the Danish Cancer Society, The Lundbeck Foundation, the Novo Nordisk Foundation, Van Andel Research Institute through the Van Andel Research Institute – Stand Up to Cancer Epigenetics Dream Team, and National Health and Medical Research Council Australia.

Researchers from DTU Health Tech identify promising possibilities for applying immunotherapy to hematological cancer patients.

In cancer treatment, immunotherapy helps the patient’s immune system fight cancer, for example through better recognition of the cancer cells, and it has proven effective in various types of cancer.

T-cells play a central role in eliminating tumors, and are the major target for cancer immunotherapies. Hematological cancers, however, present with a limited number of cancer-specific T-cells compared to solid tumors, which is why immunotherapy has not previously been efficient against hematological cancers.

An additional reservoir of cancer specific T-cells

A research team headed by Professor Sine Reker Hadrup, DTU Health Tech, now show that T-cell antigens derived from human endogenous retroviruses (HERVs) in patients with hematological malignancies can be used as an alternative source of cancer-specific antigens potentially targeted for cancer immunotherapies.

“Our study show large-scale activation of HERVs in hematological cancers and the T-cells of the immune system specifically recognize antigens derived from such HERVs. We believe that our finding of HERV-specific T-cells may have substantial therapeutic implication, as this provide an additional reservoir of cancer-specific T cells that can be targeted by ongoing immunotherapy approaches”, Assistant Professor Sunil Kumar Saini says.

Professor Sine Reker concludes: “We need to examine HERV-derived T cell recognition in more detail in immunotherapy treatment combinations to determine the direct impact of T-cell recognition of HERV-derived antigens on tumor regression. But with these results we are a step further towards developing new immunotherapy approaches.”

Read the full paper in the scientific journal Nature Communications.

HERVs

T-cell recognition of HERV derived peptides: malignant transformation and epigenetic therapies can induce expression of HERVs. Due to their viral origin, such newly expressed HERVs trigger adaptive immune response when HERV-derived peptides are presented on the cell surface in MHC class I.

 

Human endogenous retroviruses (HERVs)

HERVs, which account for approximately 8% of our genome, are reminiscent of genetic elements from exogenous retroviruses incorporated into the human genome over the course of evolution. Hence, the majority of HERVs are defective with no infectious capacity. However, due to genetic changes induced by cancer or other epigenetic factors these viral elements may get expressed and targeted by our immune system.

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