scholarly journals BRAF inhibition curtails IFN‐gamma‐inducible PD‐L1 expression and upregulates the immunoregulatory protein galectin‐1 in melanoma cells

2020 ◽  
Vol 14 (8) ◽  
pp. 1817-1832 ◽  
Author(s):  
Patryk Górniak ◽  
Maja Wasylecka‐Juszczyńska ◽  
Iwona Ługowska ◽  
Piotr Rutkowski ◽  
Anna Polak ◽  
...  
Blood ◽  
1992 ◽  
Vol 80 (11) ◽  
pp. 2817-2825 ◽  
Author(s):  
B Gansbacher ◽  
K Zier ◽  
K Cronin ◽  
PA Hantzopoulos ◽  
B Bouchard ◽  
...  

Cytokines are important modulators of host antitumor responses. Two of these cytokines, interleukin-2 (IL-2) and interferon gamma (IFN-gamma), are produced after antigen-induced activation of helper lymphocytes. The cytokines are released into the immediate vicinity where they either interact with the appropriate receptors on effector cell populations or are rapidly degraded. To mimic this physiologic release of cytokines at the effector-target site, we used retroviral vectors to transduce melanoma cells with the IL-2 or IFN-gamma cDNA. Five melanoma cell lines were transduced with IL-2- or IFN-gamma-containing vectors and secreted IL-2 at 1 to 40 U/mL/10(6) cells/24 h or IFN-gamma 1 to 8 U/mL/10(6) cells/24 h, respectively. After gamma irradiation, these cells continued to secrete cytokines for about 3 to 4 weeks. Secretion of IFN-gamma induced upregulation of major histocompatibility complex class I molecules in a subset of melanoma cell lines. IL-2 production by human melanoma xenografts induced tumor rejection in BALB/c nu/nu mice, showing the in vivo effect of this cytokine. This study shows that (1) human melanoma cells can be stably transduced with cytokine- containing retroviral vectors; (2) cytokines are secreted constitutively by the transduced tumor cells and have the expected biologic effects in vitro and in vivo; and (3) after gamma irradiation, cytokines continue to be secreted for several weeks. These data suggest that irradiated cytokine-secreting allogenic or autologous tumor cells can be used in vaccination protocols for cancer patients.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Lorey K. Smith ◽  
Tiffany Parmenter ◽  
Cathryn M. Gould ◽  
Piyush B. Madhamshettiwar ◽  
Karen E. Sheppard ◽  
...  

Abstract Identification of mechanisms underlying sensitivity and response to targeted therapies, such as the BRAF inhibitor vemurafenib, is critical in order to improve efficacy of these therapies in the clinic and delay onset of resistance. Glycolysis has emerged as a key feature of the BRAF inhibitor response in melanoma cells, and importantly, the metabolic response to vemurafenib in melanoma patients can predict patient outcome. Here, we present a multiparameter genome-wide siRNA screening dataset of genes that when depleted improve the viability and glycolytic response to vemurafenib in BRAFV600 mutated melanoma cells. These datasets are suitable for analysis of genes involved in cell viability and glycolysis in steady state conditions and following treatment with vemurafenib, as well as computational approaches to identify gene regulatory networks that mediate response to BRAF inhibition in melanoma.


1989 ◽  
Vol 170 (3) ◽  
pp. 797-810 ◽  
Author(s):  
T Wölfel ◽  
E Klehmann ◽  
C Müller ◽  
K H Schütt ◽  
K H Meyer zum Büschenfelde ◽  
...  

From the peripheral blood of the melanoma patient (AV), we derived cytolytic T lymphocyte (CTL) clones that lysed the autologous tumor line SK-MEL-29, but not autologous EBV-B cells, K562, and other tumor targets. By immunoselection experiments it was shown that the CTL clones recognized at least three different antigens on the autologous tumor cells. We demonstrate here that these melanoma antigens are presented to the CTL in association with HLA-A2. First, HLA-A2-reactive pregnancy sera as well as an mAb against HLA-A2 inhibited the CTL lysis. Second, immunoselected melanoma subclones that were resistant to lysis by CTL clones against the three antigens described were found to lack expression of HLA-A2. By sensitizing the patient's lymphocytes against an HLA-A2- melanoma clone, we established a new series of CTL clones recognizing autologous AV melanoma cells. However, efficient lysis was only seen when target cells were pretreated with IFN-gamma. The lytic activity of these CTL was selectively inhibited by an mAb against a common HLA-B determinant. These results indicate that in addition to HLA-A2, other class I antigens are involved in the recognition of AV melanoma cells by autologous CTL.


2012 ◽  
Vol 19 (3) ◽  
pp. 598-609 ◽  
Author(s):  
Xiaofeng Jiang ◽  
Jun Zhou ◽  
Anita Giobbie-Hurder ◽  
Jennifer Wargo ◽  
F. Stephen Hodi

2015 ◽  
Author(s):  
Teresa Delgado-Goni ◽  
Slawomir Wantuch ◽  
Paul Workman ◽  
Richard Marais ◽  
Martin Leach ◽  
...  

2019 ◽  
Vol 18 (6) ◽  
pp. 1096-1109 ◽  
Author(s):  
Marisa Schmitt ◽  
Tobias Sinnberg ◽  
Nicolas C. Nalpas ◽  
Annika Maass ◽  
Birgit Schittek ◽  
...  

Blood ◽  
1992 ◽  
Vol 80 (11) ◽  
pp. 2817-2825 ◽  
Author(s):  
B Gansbacher ◽  
K Zier ◽  
K Cronin ◽  
PA Hantzopoulos ◽  
B Bouchard ◽  
...  

Abstract Cytokines are important modulators of host antitumor responses. Two of these cytokines, interleukin-2 (IL-2) and interferon gamma (IFN-gamma), are produced after antigen-induced activation of helper lymphocytes. The cytokines are released into the immediate vicinity where they either interact with the appropriate receptors on effector cell populations or are rapidly degraded. To mimic this physiologic release of cytokines at the effector-target site, we used retroviral vectors to transduce melanoma cells with the IL-2 or IFN-gamma cDNA. Five melanoma cell lines were transduced with IL-2- or IFN-gamma-containing vectors and secreted IL-2 at 1 to 40 U/mL/10(6) cells/24 h or IFN-gamma 1 to 8 U/mL/10(6) cells/24 h, respectively. After gamma irradiation, these cells continued to secrete cytokines for about 3 to 4 weeks. Secretion of IFN-gamma induced upregulation of major histocompatibility complex class I molecules in a subset of melanoma cell lines. IL-2 production by human melanoma xenografts induced tumor rejection in BALB/c nu/nu mice, showing the in vivo effect of this cytokine. This study shows that (1) human melanoma cells can be stably transduced with cytokine- containing retroviral vectors; (2) cytokines are secreted constitutively by the transduced tumor cells and have the expected biologic effects in vitro and in vivo; and (3) after gamma irradiation, cytokines continue to be secreted for several weeks. These data suggest that irradiated cytokine-secreting allogenic or autologous tumor cells can be used in vaccination protocols for cancer patients.


2019 ◽  
Author(s):  
B. Bishal Paudel ◽  
Joshua E. Lewis ◽  
Keisha N. Hardeman ◽  
Corey E. Hayford ◽  
Charles J. Robbins ◽  
...  

SummaryMelanomas harboring BRAF mutations can be treated with BRAF inhibitors (BRAFi), but responses are varied and tumor recurrence is inevitable. Here, using an integrative approach of experimentation and mathematical flux balance analyses in BRAF-mutated melanoma cells, we report that elevated antioxidant capacity is linked to BRAFi sensitivity in melanoma cells. High levels of antioxidant metabolites in cells with reduced BRAFi sensitivity confirm this conclusion. By extending our analyses to other melanoma subtypes in TCGA, we predict that elevated redox capacity is a general feature of melanomas, not previously observed. We propose that redox vulnerabilities could be exploited for therapeutic benefits and identify unsuspected combination targets to enhance the effects of BRAFi in any melanoma, regardless of mutational status.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lukas Frischknecht ◽  
Christian Britschgi ◽  
Patricia Galliker ◽  
Yann Christinat ◽  
Anton Vichalkovski ◽  
...  

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