Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]

Publication Date:
2018-09-18
Publisher:
The American Association of Immunologists (AAI)
Print ISSN:
0022-1767
Electronic ISSN:
1550-6606
Topics:
Medicine
Published by:
http://www.aai.org/
_version_ 1839208186596294656
autor Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
beschreibung Immune stimulation contributes to lenalidomide’s antitumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood, and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T cell function in vitro. Whether T cell activation is required for clinical response to lenalidomide remains unclear. In this study, we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with antitumor response. Within days of starting lenalidomide, T cells increased in the tumor microenvironment and showed Th1-type polarization. Gene expression profiling of pretreatment and on-treatment lymph node biopsy specimens revealed upregulation of IFN- and many of its target genes in response to lenalidomide. The IFN-–mediated Th1 response was limited to patients achieving a clinical response defined by a reduction in lymphadenopathy. Deep sequencing of TCR genes revealed decreasing diversity of the T cell repertoire and an expansion of select clonotypes in responders. To validate our observations, we stimulated T cells and CLL cells with lenalidomide in culture and detected lenalidomide-dependent increases in T cell proliferation. Taken together, our data demonstrate that lenalidomide induced Th1 immunity in the lymph node that is associated with clinical response.
citation_standardnr 6333394
datenlieferant ipn_articles
feed_id 333
feed_publisher The American Association of Immunologists (AAI)
feed_publisher_url http://www.aai.org/
insertion_date 2018-09-18
journaleissn 1550-6606
journalissn 0022-1767
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association of Immunologists (AAI)
quelle Journal of Immunology
relation http://www.jimmunol.org/cgi/content/short/201/7/1967?rss=1
search_space articles
shingle_author_1 Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
shingle_author_2 Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
shingle_author_3 Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
shingle_author_4 Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
shingle_catch_all_1 Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
Immune stimulation contributes to lenalidomide’s antitumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood, and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T cell function in vitro. Whether T cell activation is required for clinical response to lenalidomide remains unclear. In this study, we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with antitumor response. Within days of starting lenalidomide, T cells increased in the tumor microenvironment and showed Th1-type polarization. Gene expression profiling of pretreatment and on-treatment lymph node biopsy specimens revealed upregulation of IFN- and many of its target genes in response to lenalidomide. The IFN-–mediated Th1 response was limited to patients achieving a clinical response defined by a reduction in lymphadenopathy. Deep sequencing of TCR genes revealed decreasing diversity of the T cell repertoire and an expansion of select clonotypes in responders. To validate our observations, we stimulated T cells and CLL cells with lenalidomide in culture and detected lenalidomide-dependent increases in T cell proliferation. Taken together, our data demonstrate that lenalidomide induced Th1 immunity in the lymph node that is associated with clinical response.
Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_2 Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
Immune stimulation contributes to lenalidomide’s antitumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood, and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T cell function in vitro. Whether T cell activation is required for clinical response to lenalidomide remains unclear. In this study, we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with antitumor response. Within days of starting lenalidomide, T cells increased in the tumor microenvironment and showed Th1-type polarization. Gene expression profiling of pretreatment and on-treatment lymph node biopsy specimens revealed upregulation of IFN- and many of its target genes in response to lenalidomide. The IFN-–mediated Th1 response was limited to patients achieving a clinical response defined by a reduction in lymphadenopathy. Deep sequencing of TCR genes revealed decreasing diversity of the T cell repertoire and an expansion of select clonotypes in responders. To validate our observations, we stimulated T cells and CLL cells with lenalidomide in culture and detected lenalidomide-dependent increases in T cell proliferation. Taken together, our data demonstrate that lenalidomide induced Th1 immunity in the lymph node that is associated with clinical response.
Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_3 Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
Immune stimulation contributes to lenalidomide’s antitumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood, and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T cell function in vitro. Whether T cell activation is required for clinical response to lenalidomide remains unclear. In this study, we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with antitumor response. Within days of starting lenalidomide, T cells increased in the tumor microenvironment and showed Th1-type polarization. Gene expression profiling of pretreatment and on-treatment lymph node biopsy specimens revealed upregulation of IFN- and many of its target genes in response to lenalidomide. The IFN-–mediated Th1 response was limited to patients achieving a clinical response defined by a reduction in lymphadenopathy. Deep sequencing of TCR genes revealed decreasing diversity of the T cell repertoire and an expansion of select clonotypes in responders. To validate our observations, we stimulated T cells and CLL cells with lenalidomide in culture and detected lenalidomide-dependent increases in T cell proliferation. Taken together, our data demonstrate that lenalidomide induced Th1 immunity in the lymph node that is associated with clinical response.
Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_catch_all_4 Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
Immune stimulation contributes to lenalidomide’s antitumor activity. Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of mature, autoreactive B cells in secondary lymphoid tissues, blood, and bone marrow and progressive immune dysfunction. Previous studies in CLL indicated that lenalidomide can repair defective T cell function in vitro. Whether T cell activation is required for clinical response to lenalidomide remains unclear. In this study, we report changes in the immune microenvironment in patients with CLL treated with single-agent lenalidomide and associate the immunologic effects of lenalidomide with antitumor response. Within days of starting lenalidomide, T cells increased in the tumor microenvironment and showed Th1-type polarization. Gene expression profiling of pretreatment and on-treatment lymph node biopsy specimens revealed upregulation of IFN- and many of its target genes in response to lenalidomide. The IFN-–mediated Th1 response was limited to patients achieving a clinical response defined by a reduction in lymphadenopathy. Deep sequencing of TCR genes revealed decreasing diversity of the T cell repertoire and an expansion of select clonotypes in responders. To validate our observations, we stimulated T cells and CLL cells with lenalidomide in culture and detected lenalidomide-dependent increases in T cell proliferation. Taken together, our data demonstrate that lenalidomide induced Th1 immunity in the lymph node that is associated with clinical response.
Aue, G., Sun, C., Liu, D., Park, J.-H., Pittaluga, S., Tian, X., Lee, E., Soto, S., Valdez, J., Maric, I., Stetler-Stevenson, M., Yuan, C., Nakamura, Y., Muranski, P., Wiestner, A.
The American Association of Immunologists (AAI)
0022-1767
00221767
1550-6606
15506606
shingle_title_1 Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
shingle_title_2 Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
shingle_title_3 Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
shingle_title_4 Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
timestamp 2025-07-31T23:46:48.810Z
titel Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
titel_suche Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia [IMMUNOTHERAPY AND VACCINES]
topic WW-YZ
uid ipn_articles_6333394