Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/29552
Title: Chemotherapy Induces Intra-Tumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T Cell Infiltration and Tumor Control
Authors: HONG LI WEN MICHELLE
Keywords: Chemotherapy, Melanoma, T cell, Chemokine, Tumor
Issue Date: 19-Jul-2011
Source: HONG LI WEN MICHELLE (2011-07-19). Chemotherapy Induces Intra-Tumoral Expression of Chemokines in Cutaneous Melanoma, Favoring T Cell Infiltration and Tumor Control. ScholarBank@NUS Repository.
Abstract: T cell infiltration is known to impact tumour growth and is associated with cancer patient survival. However, the molecular cues that favour T cell infiltration remain largely undefined. Here, using a genetically-engineered mouse model of melanoma, we show that CXCR3 ligands and CCL5 synergize to attract effector T cells into cutaneous metastases, and their expression inhibits tumour growth. In melanoma patients, these chemokines are also up-regulated in chemotherapy-sensitive lesions following chemotherapy, and correlate with T cell infiltration, tumour control and patient survival. Mechanistically, we found that dacarbazine, temozolomide and cisplatin induce expression of these T cell-attracting chemokines in several human melanoma cell lines in vitro. These data identify the induction of intra-tumoral expression of chemokines as a novel cell-extrinsic mechanism of action of chemotherapy that results in the recruitment of immune cells with anti-tumour activity. Additionally, we report a new reporter mouse melanoma model that enables visualization of spontaneous tumour development by in vivo bioluminescence imaging. This model will facilitate testing of future chemo-immunotherapeutic strategies against melanoma.
URI: http://scholarbank.nus.edu.sg/handle/10635/29552
Appears in Collections:Ph.D Theses (Open)

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