Grant: Fellowship - Priority Announcement: Melanoma (SHOPP)

The incidence of melanoma in North America is rising. In 2011 alone, 75,000 cases will have been newly diagnosed and 14,000 will have died. Metastatic melanoma has a very poor prognosis with less than 5 year survival. Recently, ipimulimab, a CTLA-4 inhibitor which modulates patients' immune response, and vemurafenib, which targets melanoma cells with the BRAF mutation, have improved survival in metastatic melanoma patients. However, almost all patients will eventually develop resistance to these drugs and better treatment strategies are needed to overcome the limitations of current therapeutic approaches. T lymphocytes are crucial in mounting anti-tumour immune responses. Therapies which increase T-cell responses such as CTLA-4 inhibitors and adoptive T cell therapy whereby T lymphocytes are isolated from a patient and expanded in ex vivo culture and reinfused into the same patient have produced long lasting tumour control in 20% of patients. Evaluation of tumour tissues has also suggested that increase in number of "tumour infiltrating lymphocytes" (TILs) after treatment with ipimulimab correlated with patients' clinical response. The role of TILs in patients receiving BRAF inhibitors such as vemurafenib, however, has not been widely studied and it is unknown how critical the immune response is for patients to respond to vemurafenib. Studying TILs in the tumour microenvironment in vemurafenib treated patients may uncover the underlying immune mechanisms which modulates response and resistance to BRAF inhibition and also shed light on new therapeutic strategies that may be used to optimize current treatment paradigm. The proposed study is novel and unique in seeking to characterize TILs (phenotypic subtypes and function) in paired tumour tissues obtained before and after vemurafenib treatment in sufficient number of patients to gain enough data on TILs to inform future studies.