How can we know if the anti-PD1 therapy will work in certain melanoma patients?

NK Cells: potential predictive marker for response to anti-PD1 therapy in melanoma patients.

An interesting research was presented by Australian scientist and that we will talk about in the next lines, along with the incidence of melanoma in Australia where it is commonly affected by this dangerous disease.

Australia is one of the most affected countries for mortality by melanoma. The estimated number of new cases of melanoma skin cancer diagnosed in 2018 are 14,320, in which 8,653 are males and 5,667 are females. The estimated number of deaths were 1,905, leading again the men group (Source: Government of Australia, Melanoma of the skin statistics, 04/Sep/2018). Back in 2014, the melanoma skin cancer was the 4th most commonly diagnosed cancer in Australia and this amount increased even more. It is an aggressive disease that so far, doesn’t have a standard scheme of treatment compared to other types of cancer. Moreover, chemotherapy unfortunately is not an option, since it has shown low efficacy rates in melanoma tumors. It is important to know which the microenvironment in with the tumor is, so we can know more about the mechanism in with the melanoma tumors grow.

The treatment for this aggressive disease is Immunotherapy. The most common approach used is the Anti-PD1 therapy, such as Pembrolizumab and Nivolumab therapies. Despite the success of these therapies, resistance is still an issue. The resistance may be caused by additional immune evasive mechanisms, such as the downregulation of MHC Class I molecules controlled by the CD8+ T cells, giving as a result the downregulation of antigen presentation. In addition, as part of the innate immune system, the natural killer (NK) cells actively look for this type of cells that downregulate the MHC Class I. Therefore, in the study presented by Scolyer et al (2017), they were trying to determine if the density and phenotype of the NK cells differed in the tissue of stage IV melanoma patients before the immunotherapy. They measured the density of NK cells in melanoma tissue from 13 good and 12 poor responders to anti-PD1 therapy and also they were phenotyped according to their activation and maturation status using multiplex immunofluorescent staining for CD16a, CD56 and CD3.

Their results showed that:

  • Good responders had the highest number of CD16+ NK cells that poor responders in the intratumoural and peritumoural areas
  • And that the CD16+, CD56-, and CD3- cells were significantly different between the good and poor responders.

According to what was shown from these results, they conclude that CD16+ NK cells play a role in anti tumor immunity through the interaction of tumor cells that have antibodies.