Why is melanoma immunogenic

Home » Cancer Topics » Skin Cancer. How can we make a cold tumor hot, or how can we define better upfront which tumors are hot? The study included patients who received TVEC; 80 of these whom were followed for at least 3 months after treatment and had treatment response data available for analysis. Of the 31 patients who achieved a complete local response, 29 patients had no evidence of disease at their last recorded follow-up appointment.

Some cancers are known to be highly immunogenic—that is, able to provoke an immune response. Melanoma, kidney cancer, and non-small cell lung cancer are three such immunogenic cancers. Not coincidentally, these are also the cancers that have responded most dramatically to existing immunotherapies, such as checkpoint inhibitors. Because the immune system has already recognized these cancers, this pre-existing immune response can be strengthened with immunotherapies, generating a more powerful anti-cancer response.

Other tumor types are notoriously resistant to immunotherapies, pancreatic cancer being the prime example. But what if there were a way to jumpstart an immune response to pancreatic cancer? Could this cancer type then become a potential target for immunotherapies—in particular, the promising anti-PD-1 checkpoint inhibitors that are currently making such waves in the oncology community?

Researchers at the Johns Hopkins School of Medicine have now begun to crack this nut. In particular, the authors show that the vaccine triggers recruitment of tumor infiltrating lymphocytes TILs to the site of the tumor. Normally, in unvaccinated patients, pancreatic tumors have very few lymphocytes present; indeed, this immune ghost town provides the explanation why the tumor is non-immunogenic. Moreover, these TILs show molecular signs of being activated against pancreatic tumor antigens.

In effect, the researchers have shown that pancreatic cancer can be converted from a non-immunogenic tumor type to an immunogenic one. As the authors note, these promising results raise the possibility that pancreatic cancer could be treated with immunotherapies that combine, for example, cancer vaccines and checkpoint inhibitors.

In fact, such clinical trials are already under way. Melanoma vaccines oncolytic viruses, oncolytic immunotherapy. Untreated distant lesions regressed in 13 of 22 evaluable patients. Talimogene laherparepvec T-VEC is directly injected into melanoma lesions. It is engineered from herpes simplex virus 1 HSV-1 to replicate inside tumor cells and cause immunogenic cell death ICD. Lysis of cancer cells in this fashion releases tumor-derived antigens, as well as granulocyte-macrophage colony-stimulating factor GM-CSF , to stimulate an adaptive immune response.

Median overall survival was Responses were seen in patients who had previously been treated with checkpoint inihibitors. TLR activation alerts the immune system to pathogens and initiates both innate and adaptive immune responses. It is an immunogenic tumor. While targeting programmed death 1 PD-1 is a great start, it is not a home run. There are a lot of ways to modify tumors and make PD-1 more effective.

T-VEC [talimogene laherparepvec] and other vaccines that use multiple tumor-associated antigens are particularly exciting. Just as oncologists have learned that cytotoxic chemotherapy agents can synergize in the management of cancer, combining immunotherapies may be the best way to exploit their clinical value.

Multiple clinical trials of checkpoint inhibitors together with therapeutic vaccines and other immunotherapeutic strategies are under way to learn whether or not they can counteract immune system tolerance, improve antitumor immunity, and extend survival for patients with melanoma. Stanton looks forward to moving these combination strategies into patients with earlier stages of cancer. View the entire Special Report on Immunotherapy. Featured Clinical Focus. March 24, Lisa Raedler, PhD.

The Challenge of Melanoma Melanoma is the most deadly skin cancer. Figure 1. Clinical Pearls Repeated presentation of tumor-associated antigens is the first critical step to inducing an adaptive immune or T-cell response.

Melanoma is an immunogenic tumor. In addition to checkpoint inhibitors, oncolytic vaccines and other developmental immunotherapies offer the possibility of durable remission. References Skin Cancer Foundation. What is melanoma? Accessed March 10, National Cancer Institute web site.