AGING AND PD-1 & PD-L1 GENE EXPRESSION: MARKERS OF IMMUNOSENESCENCE?
(Abstract release date: 05/19/16)
EHA Library. BRON D. 06/09/16; 134674; PB1774
Prof. Dr. Dominique BRON
Contributions
Contributions
Abstract
Abstract: PB1774
Type: Publication Only
Background
Aging is characterized by a progressive decline in immune surveillance that favors infection and cancer development. Cancer cells can escape immune surveillance by upregulating inhibitory immune checkpoint such as PD-1 and PD-L1. High surface expression of PD-1 was reported in association with T-cell exhaustion. The PD-1/PD-L1 axis inhibits the immune response leading to anergy of lymphocytes.
Aims
In this study, we examined the expression of PD-1 and PD-L1 genes in lymphocytes subsets according to age.
Methods
Lymphocyte subsets (CD3+CD4+; CD3+CD8+, CD19+) were isolated using the MACS isolation system from PBMC of healthy donors (HD) and Chronic Lymphocytic Leukemia (CLL) patients. PD-1, PD-L1, IL4 and IFNɣ were quantified by qRT-PCR for each purified lymphocyte subset.
Results
PD-1, PD-L1, IL4 and IFNɣ gene expression was studied using qRT-PCR to evaluate 28 HDs [14 HDs under 50y (median-: 38) and 14 HDs above 50y (median: 62)] compared with 23 untreated CLL patients (median age: 69). The purity of each lymphocyte subset was 95%>99%. PD-1 was significantly up-regulated in most lymphocyte subsets in the older group: CD4+, CD8+ T cells and CD19+ B cells (p=0.015; 0.02 and 0.01, respectively). Compared with a similar age group of HDs, PD-1 expression was strongly upregulated in CD4+, CD8+ and CD19+ subsets of CLL patients (p=0.001; 0.002 and <0.001). High PD-L1 expression was correlated with age in the normal B lymphocytes (p=0.046). The leukemic B cells also expressed higher levels of PD-L1 than circulating normal B cells as compared with the older group of healthy donors (p=0.001).In order to further investigate the PD-1/PD-L1 axis contribution to T cell dysfunction, we have checked for the expression of IL4 and IFNɣ genes in CD4+ and CD8+ lymphocytes subsets, respectively. A significant down-regulation of IL4 and IFNɣ (p=0.008 and 0.001) in CLL patients was also demonstrated.
Conclusion
1) PD-1 and PD-L1 gene expression is correlated with aging 2) Upregulation PD-L1 is even more pronounced in leukemic B cells, suggesting a potential benefit of anti PD-1 / PD-L1 drugs in CLL patients 3) In CLL patients, upregulation of PD1 and lower expression of IL4 and IFNɣ gene are observed in CD4+ and CD8+ T cells.
Session topic: E-poster
Keyword(s): Elderly, Genetic instability, Immune deficiency
Type: Publication Only
Background
Aging is characterized by a progressive decline in immune surveillance that favors infection and cancer development. Cancer cells can escape immune surveillance by upregulating inhibitory immune checkpoint such as PD-1 and PD-L1. High surface expression of PD-1 was reported in association with T-cell exhaustion. The PD-1/PD-L1 axis inhibits the immune response leading to anergy of lymphocytes.
Aims
In this study, we examined the expression of PD-1 and PD-L1 genes in lymphocytes subsets according to age.
Methods
Lymphocyte subsets (CD3+CD4+; CD3+CD8+, CD19+) were isolated using the MACS isolation system from PBMC of healthy donors (HD) and Chronic Lymphocytic Leukemia (CLL) patients. PD-1, PD-L1, IL4 and IFNɣ were quantified by qRT-PCR for each purified lymphocyte subset.
Results
PD-1, PD-L1, IL4 and IFNɣ gene expression was studied using qRT-PCR to evaluate 28 HDs [14 HDs under 50y (median-: 38) and 14 HDs above 50y (median: 62)] compared with 23 untreated CLL patients (median age: 69). The purity of each lymphocyte subset was 95%>99%. PD-1 was significantly up-regulated in most lymphocyte subsets in the older group: CD4+, CD8+ T cells and CD19+ B cells (p=0.015; 0.02 and 0.01, respectively). Compared with a similar age group of HDs, PD-1 expression was strongly upregulated in CD4+, CD8+ and CD19+ subsets of CLL patients (p=0.001; 0.002 and <0.001). High PD-L1 expression was correlated with age in the normal B lymphocytes (p=0.046). The leukemic B cells also expressed higher levels of PD-L1 than circulating normal B cells as compared with the older group of healthy donors (p=0.001).In order to further investigate the PD-1/PD-L1 axis contribution to T cell dysfunction, we have checked for the expression of IL4 and IFNɣ genes in CD4+ and CD8+ lymphocytes subsets, respectively. A significant down-regulation of IL4 and IFNɣ (p=0.008 and 0.001) in CLL patients was also demonstrated.
Conclusion
1) PD-1 and PD-L1 gene expression is correlated with aging 2) Upregulation PD-L1 is even more pronounced in leukemic B cells, suggesting a potential benefit of anti PD-1 / PD-L1 drugs in CLL patients 3) In CLL patients, upregulation of PD1 and lower expression of IL4 and IFNɣ gene are observed in CD4+ and CD8+ T cells.
Session topic: E-poster
Keyword(s): Elderly, Genetic instability, Immune deficiency
Abstract: PB1774
Type: Publication Only
Background
Aging is characterized by a progressive decline in immune surveillance that favors infection and cancer development. Cancer cells can escape immune surveillance by upregulating inhibitory immune checkpoint such as PD-1 and PD-L1. High surface expression of PD-1 was reported in association with T-cell exhaustion. The PD-1/PD-L1 axis inhibits the immune response leading to anergy of lymphocytes.
Aims
In this study, we examined the expression of PD-1 and PD-L1 genes in lymphocytes subsets according to age.
Methods
Lymphocyte subsets (CD3+CD4+; CD3+CD8+, CD19+) were isolated using the MACS isolation system from PBMC of healthy donors (HD) and Chronic Lymphocytic Leukemia (CLL) patients. PD-1, PD-L1, IL4 and IFNɣ were quantified by qRT-PCR for each purified lymphocyte subset.
Results
PD-1, PD-L1, IL4 and IFNɣ gene expression was studied using qRT-PCR to evaluate 28 HDs [14 HDs under 50y (median-: 38) and 14 HDs above 50y (median: 62)] compared with 23 untreated CLL patients (median age: 69). The purity of each lymphocyte subset was 95%>99%. PD-1 was significantly up-regulated in most lymphocyte subsets in the older group: CD4+, CD8+ T cells and CD19+ B cells (p=0.015; 0.02 and 0.01, respectively). Compared with a similar age group of HDs, PD-1 expression was strongly upregulated in CD4+, CD8+ and CD19+ subsets of CLL patients (p=0.001; 0.002 and <0.001). High PD-L1 expression was correlated with age in the normal B lymphocytes (p=0.046). The leukemic B cells also expressed higher levels of PD-L1 than circulating normal B cells as compared with the older group of healthy donors (p=0.001).In order to further investigate the PD-1/PD-L1 axis contribution to T cell dysfunction, we have checked for the expression of IL4 and IFNɣ genes in CD4+ and CD8+ lymphocytes subsets, respectively. A significant down-regulation of IL4 and IFNɣ (p=0.008 and 0.001) in CLL patients was also demonstrated.
Conclusion
1) PD-1 and PD-L1 gene expression is correlated with aging 2) Upregulation PD-L1 is even more pronounced in leukemic B cells, suggesting a potential benefit of anti PD-1 / PD-L1 drugs in CLL patients 3) In CLL patients, upregulation of PD1 and lower expression of IL4 and IFNɣ gene are observed in CD4+ and CD8+ T cells.
Session topic: E-poster
Keyword(s): Elderly, Genetic instability, Immune deficiency
Type: Publication Only
Background
Aging is characterized by a progressive decline in immune surveillance that favors infection and cancer development. Cancer cells can escape immune surveillance by upregulating inhibitory immune checkpoint such as PD-1 and PD-L1. High surface expression of PD-1 was reported in association with T-cell exhaustion. The PD-1/PD-L1 axis inhibits the immune response leading to anergy of lymphocytes.
Aims
In this study, we examined the expression of PD-1 and PD-L1 genes in lymphocytes subsets according to age.
Methods
Lymphocyte subsets (CD3+CD4+; CD3+CD8+, CD19+) were isolated using the MACS isolation system from PBMC of healthy donors (HD) and Chronic Lymphocytic Leukemia (CLL) patients. PD-1, PD-L1, IL4 and IFNɣ were quantified by qRT-PCR for each purified lymphocyte subset.
Results
PD-1, PD-L1, IL4 and IFNɣ gene expression was studied using qRT-PCR to evaluate 28 HDs [14 HDs under 50y (median-: 38) and 14 HDs above 50y (median: 62)] compared with 23 untreated CLL patients (median age: 69). The purity of each lymphocyte subset was 95%>99%. PD-1 was significantly up-regulated in most lymphocyte subsets in the older group: CD4+, CD8+ T cells and CD19+ B cells (p=0.015; 0.02 and 0.01, respectively). Compared with a similar age group of HDs, PD-1 expression was strongly upregulated in CD4+, CD8+ and CD19+ subsets of CLL patients (p=0.001; 0.002 and <0.001). High PD-L1 expression was correlated with age in the normal B lymphocytes (p=0.046). The leukemic B cells also expressed higher levels of PD-L1 than circulating normal B cells as compared with the older group of healthy donors (p=0.001).In order to further investigate the PD-1/PD-L1 axis contribution to T cell dysfunction, we have checked for the expression of IL4 and IFNɣ genes in CD4+ and CD8+ lymphocytes subsets, respectively. A significant down-regulation of IL4 and IFNɣ (p=0.008 and 0.001) in CLL patients was also demonstrated.
Conclusion
1) PD-1 and PD-L1 gene expression is correlated with aging 2) Upregulation PD-L1 is even more pronounced in leukemic B cells, suggesting a potential benefit of anti PD-1 / PD-L1 drugs in CLL patients 3) In CLL patients, upregulation of PD1 and lower expression of IL4 and IFNɣ gene are observed in CD4+ and CD8+ T cells.
Session topic: E-poster
Keyword(s): Elderly, Genetic instability, Immune deficiency
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