The Immune System in Skin Cancers

Professor Ilkka Harvima and Dr Hanna Siiskonen, Department of Dermatology, University of Eastern Finland and Kuopio University Hospital

 

 

 

 

 

 

 

 

 

 

Melanoma and non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma) have been increasing in population in an epidemic fashion during the last 4 decades, and these cancer types cause a significant burden to the health care system. Ultraviolet radiation from the sun is the essential factor in skin carcinogenesis through induction of immunosuppression and DNA damage.

The immune system and peritumoral stroma can play an essential role in the growth and invasion of cancers. The role of the immune system is emphasized in organ transplant recipients that have a highly increased risk for skin cancers due to effective immunosuppressive treatment. Increased number of cells of the immune system is a typical feature of a variety of skin cancer types. However, their proinflammatory or immunosuppressive function in tumorigenesis is not sufficiently known.

The research project, constituting a part of the North-Savo Skin Cancer Program (NoSCaP), is aimed at enhancing secondary prevention of skin cancers through identification of patients at increased risk for skin cancers. An especial focus of the project is to identify the immunomarkers that can predict skin cancer development. In order to achieve this goal, NoSCaP will be using skin cancer material collected at Kuopio University Hospital in 2000-2013 and subsequently transferred to the Biobank of Eastern Finland. In addition, a follow-up project of patients at increased risk for skin cancers has been initiated. Skin biopsies and blood samples collected from these patients at the first visit at the dermatological policlinic will be analyzed for a variety of immunomarkers.

10 SELECTED PUBLICATIONS

1. Fischer M, Harvima IT, Carvalho RFS, Möller C, Naukkarinen A, Enblad G, Nilsson G. Mast cell CD30 ligand is up-regulated in cutaneous inflammations and mediates degranulation-independent chemokine secretion. J Clin Invest 116: 2748-2756, 2006.

2. Diaconu N-C, Rummukainen J, Mättö M, Naukkarinen A, Harvima RJ, Pelkonen J, Harvima IT. Cervical squamous carcinoma cells are resistant to the combined action of tumor necrosis factor-α and histamine whereas normal keratinocytes undergo cytolysis. BMC Cancer 8: 46, 2008.

3. Karlberg M, Ekoff M, Huang DC, Mustonen P, Harvima IT, Nilsson G. The BH3-mimetic ABT-737 induces mast cell apoptosis in vitro and in vivo - potential for therapeutics. J Immunol 185: 2555-2562, 2010.

4. Ekoff AME, Lyberg AKE Arvidsson M, Rak S, Reed JC, Harvima IT, Nilsson GP. Anti-apoptotic Bfl-1 is the major effector in activation-induced human mast cell survival. PLoS ONE 7(6):e39117, 2012.

5. Harvima IT, Levi-Schaffer F, Draber P, Friedman S, Polakovicova I, Gibbs BF, Blank U, Nilsson G, Maurer M. Molecular targets on mast cells and basophils for novel therapies. J Allergy Clin Immunol 134: 530-544, 2014.

6. Siiskonen H, Poukka M, Bykachev A, Tyynelä-Korhonen K, Sironen R, Pasonen-Seppänen S, Harvima IT. Low numbers of tryptase+ and chymase+ mast cells associated with reduced survival and advanced tumor stage in melanoma. Melanoma Res 25: 479-485, 2015.

7. Haimakainen S, Kaukinen AP, Suttle MM, Pelkonen J, Harvima IT. CD40 ligand is increased in mast cells in psoriasis and actinic keratosis, but less so in epithelial skin carcinomas. Cancer Invest 35: 143-151, 2017.

8. Gupta K, Harvima IT. Mast cell-neural interactions contribute to pain and itch. Immunol Rev 282: 168-187, 2018.

9. Lipitsä T, Siiskonen H, Naukkarinen A, Harvima IT. Mast cell chymase degrades fibrinogen and fibrin. Br J Dermatol 181: 296-303, 2019.

10. Rahkola D, Laitala J, Siiskonen H, Pelkonen J, Harvima IT. Mast cells are a marked source for complement C3 products that associate with increased CD11b-positive cells in keratinocyte skin carcinomas. Cancer Invest 37: 73-84, 2019.