CXCR1 as a novel target for directing reactive T cells toward melanoma: implications for adoptive cell transfer immunotherapy

Chemokine receptor engineering of T cells with CXCR2 improves homing towards subcutaneous human melanomas in xenograft mouse model

“…The remaining 7 chemokines analyzed by luminex (CCL5, CCL17, CCL22, CXCL9, CXCL10, CXCL11 and CXCL16) were found at negligible levels after 48 h. This is most likely due to secretion of cytokines, growth factors and chemokines by stromal cells in the tumor microenvironment, which are not represented in our luminex assay, rather than by cancer cells themselves. This is in line with findings by others, that while IHC sections or RT-PCR analyses of tumor biopsies show a wide expression of these chemokine, 18 , 29 , 30 the majority of melanoma cell lines only secretes a limited variety of chemokines, among which CXCL8/IL8 are consistently secreted at high levels. 18 , 30 It does however limit our ability to test a combination of chemokine receptors beyond CXCR2, by ACT of xenograft tumors, as the model would lack the cognate chemokine ligands.…”

“…This is in line with findings by others, that while IHC sections or RT-PCR analyses of tumor biopsies show a wide expression of these chemokine, 18 , 29 , 30 the majority of melanoma cell lines only secretes a limited variety of chemokines, among which CXCL8/IL8 are consistently secreted at high levels. 18 , 30 It does however limit our ability to test a combination of chemokine receptors beyond CXCR2, by ACT of xenograft tumors, as the model would lack the cognate chemokine ligands.…”

“…CCR2, 40 CXCR1, 30 CXCR2 34 , 35 and CXCR3 41 transduction of T and NK cells have been pursued in pre-clinical models, showing increased homing to tumor site, and as a result improved tumor control, setting the stage for human trials. A phase I/II study of lymphodepletion plus ACT with CXCR2 and Nerve Growth Factor Receptor (NGFR) transduced TILs are currently being investigated in patients with MM (NCT01740557).…”

T-cells “à la CAR-T(e)” – Genetically engineering T-cell response against cancer

“…This applies also to T-cell engineering. To overcome the lack of trafficking of specific T cells to tumors, it is possible to engineer them to express chemokine receptors such as CXCR2 [252,253], CCR4 [253], CCR2 [254,255] or CXCR1 as we previously showed [256] (Fig.1).…”

Adoptive T-Cell Therapy: Optimizing Chemokine Receptor-Mediated Homing of T Cells in Cancer Immunotherapy

“…Cytotoxicity and interferon secretion activity are unaltered by CXCR1 expression profi le. Taken together, these results mark CXCR1 as a candidate for genetic manipulations to enhance the traffi cking of adoptively transferred T cells [ 171 ]. This approach is complementary and potentially synergistic with other genetic strategies designed to enhance antitumor potency.…”