Study Explains Why Melanoma, Other Cancers Evade and Resist Immunotherapy

Cutaneous melanoma is the most aggressive skin cancer type and it is characterized by manifesting diverse mutations. Under normal circumstances, several of these mutations could be identified as threats by the immune system, but in this type of cancer, this doesn’t happen. Consequently, most patients are unresponsive to immunotherapy. This challenge has baffled oncology researchers for years.

Now new research conducted by CNIO Melanoma Group located at the National Cancer Research Center in Spain has discovered the mechanism through which aggressive tumors like cutaneous melanoma evade the immune system in a way that isn’t expected.

The study team, headed by Marisol Soengas, explains why melanoma spreads and forms metastases that are unresponsive to existing immunotherapies. Xavier Catena, the study’s first author, is based at Sweden’s University of Lund. The researchers discovered that cutaneous melanoma secretes proteins called Midkines that reduce dendritic immune cells, cells responsible for recognizing tumor cells.

Midkines don’t just compromise dendritic cells; they also go a step further to reprogram how these immune cells work so that they not only cease to recognize cancerous cells but instead support their proliferation, according to the study.

Soengas explains that they found that Midkines serve a dual purpose of acting as a shield against the immune system and also accelerating tumor cell spread.

In conventional language, dendritic immune cells do the work of sentinels in groups of immune cells that patrol the body. These sentinels are the first to identify foreign molecules within tumors, viruses and bacteria. This information is then relayed to cytotoxic T lymphocytes, which then attack and kill those foreign cells identified. In cutaneous melanoma, this process is disrupted by Midkines through curbing dendritic cell numbers and then reprogramming them for the cancer’s benefit.

The researchers explain that their findings show that melanoma cools down and then perverts the immune system very early during cancer’s development and does the same thing throughout the body, with the result that it becomes complicated to develop novel therapies against these cancers.

Using animal models, the team of researchers discovered that blocking Midkine activity makes dendritic-focused vaccines more effective. Additionally, blocking Midkines from doing what they do facilitates immune checkpoint inhibitors, a common type of immunotherapy, to deliver expected clinical outcomes.

The CNIO team also analyzed several data sets taken from large patient cohorts and saw that gene signatures connected to Midkines resulted in worse prognosis for the patients. Midkine activity manifested in not just cutaneous melanoma but also in other cancers like adrenal gland, breast, endometrium, mesothelium, lung and other cancers.

These insights could provide immune-oncology firms like Calidi Biotherapeutics Inc. (NYSE American: CLDI) with valuable factors to consider in their quest to commercialize the next generation of immune therapies against solid tumors.

About BioMedWire

BioMedWire (“BMW”) is a specialized communications platform with a focus on the latest developments in the Biotechnology (BioTech), Biomedical Sciences (BioMed) and Life Sciences sectors. It is one of 70+ brands within the Dynamic Brand Portfolio @ IBN that delivers: (1) access to a vast network of wire solutions via InvestorWire to efficiently and effectively reach a myriad of target markets, demographics and diverse industries; (2) article and editorial syndication to 5,000+ outlets; (3) enhanced press release enhancement to ensure maximum impact; (4) social media distribution via IBN to millions of social media followers; and (5) a full array of tailored corporate communications solutions. With broad reach and a seasoned team of contributing journalists and writers, BMW is uniquely positioned to best serve private and public companies that want to reach a wide audience of investors, influencers, consumers, journalists and the general public. By cutting through the overload of information in today’s market, BMW brings its clients unparalleled recognition and brand awareness.

BMW is where breaking news, insightful content and actionable information converge.

To receive SMS alerts from BioMedWire, “Biotech” to 888-902-4192 (U.S. Mobile Phones Only)

For more information, please visit https://www.BioMedWire.com

Please see full terms of use and disclaimers on the BioMedWire website applicable to all content provided by BMW, wherever published or re-published: https://www.BioMedWire.com/Disclaimer

BioMedWire
San Francisco, CA
www.BioMedWire.com
415.949.5050 Office
Editor@BioMedWire.com

BioMedWire is powered by IBN