Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations
To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed/refractory (r/r) cHL and wer...
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2021
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oai:doaj.org-article:0435aea250c1445fb445bd9fce6f207d2021-11-25T17:02:33ZImmunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations10.3390/cancers132256762072-6694https://doaj.org/article/0435aea250c1445fb445bd9fce6f207d2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5676https://doaj.org/toc/2072-6694To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed/refractory (r/r) cHL and were treated with nivolumab. Repeated samples were obtained in 15 patients at relapse or disease progression after immunotherapy. Median follow-up was 55 (13–63) months. The best overall response rate and progression-free survival (PFS) were analyzed depending on the expression of CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT, CD163/c-maf in the tumor microenvironment in primary and sequential biopsies. The combination of CD163/c-maf antibodies was used for the identification of M2 macrophages (M2). A low number of macrophages in primary samples was associated with inferior PFS during nivolumab treatment (for CD163-positive cells <i>p</i> = 0.0086; for CD68-positive cells <i>p</i> = 0.037), while a low number of M2 with higher PFS (<i>p</i> = 0.014). Complete response was associated with a lower level of M2 (<i>p</i> = 0.011). In sequential samples (before and after nivolumab therapy) an increase in PD-1 (<i>p</i> = 0.011) and LAG-3 (<i>p</i> = 0.0045) and a depletion of CD68 (<i>p</i> = 0.057) and CD163 (<i>p</i> = 0.0049)-positive cells were observed. The study expands understanding of the cHL microenvironment structure and dynamics during nivolumab therapy in patients with r/r cHL.Artem GusakLiudmila FedorovaKirill LepikNikita VolkovMarina PopovaIvan MoiseevNatalia MikhailovaVadim BaykovAlexander KulaginMDPI AGarticlerelapsed or refractory classic Hodgkin lymphomanivolumabimmune checkpointsmacrophagesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5676, p 5676 (2021) |
| institution |
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| collection |
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| topic |
relapsed or refractory classic Hodgkin lymphoma nivolumab immune checkpoints macrophages Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
relapsed or refractory classic Hodgkin lymphoma nivolumab immune checkpoints macrophages Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Artem Gusak Liudmila Fedorova Kirill Lepik Nikita Volkov Marina Popova Ivan Moiseev Natalia Mikhailova Vadim Baykov Alexander Kulagin Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations |
| description |
To date, the impact of the tumor microenvironment on the prognosis of patients with classic Hodgkin lymphoma (cHL) during anti-PD-1 therapy has been studied insufficiently. This retrospective study included 61 primary samples of lymph nodes from patients who had relapsed/refractory (r/r) cHL and were treated with nivolumab. Repeated samples were obtained in 15 patients at relapse or disease progression after immunotherapy. Median follow-up was 55 (13–63) months. The best overall response rate and progression-free survival (PFS) were analyzed depending on the expression of CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT, CD163/c-maf in the tumor microenvironment in primary and sequential biopsies. The combination of CD163/c-maf antibodies was used for the identification of M2 macrophages (M2). A low number of macrophages in primary samples was associated with inferior PFS during nivolumab treatment (for CD163-positive cells <i>p</i> = 0.0086; for CD68-positive cells <i>p</i> = 0.037), while a low number of M2 with higher PFS (<i>p</i> = 0.014). Complete response was associated with a lower level of M2 (<i>p</i> = 0.011). In sequential samples (before and after nivolumab therapy) an increase in PD-1 (<i>p</i> = 0.011) and LAG-3 (<i>p</i> = 0.0045) and a depletion of CD68 (<i>p</i> = 0.057) and CD163 (<i>p</i> = 0.0049)-positive cells were observed. The study expands understanding of the cHL microenvironment structure and dynamics during nivolumab therapy in patients with r/r cHL. |
| format |
article |
| author |
Artem Gusak Liudmila Fedorova Kirill Lepik Nikita Volkov Marina Popova Ivan Moiseev Natalia Mikhailova Vadim Baykov Alexander Kulagin |
| author_facet |
Artem Gusak Liudmila Fedorova Kirill Lepik Nikita Volkov Marina Popova Ivan Moiseev Natalia Mikhailova Vadim Baykov Alexander Kulagin |
| author_sort |
Artem Gusak |
| title |
Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations |
| title_short |
Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations |
| title_full |
Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations |
| title_fullStr |
Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations |
| title_full_unstemmed |
Immunosuppressive Microenvironment and Efficacy of PD-1 Inhibitors in Relapsed/Refractory Classic Hodgkin Lymphoma: Checkpoint Molecules Landscape and Macrophage Populations |
| title_sort |
immunosuppressive microenvironment and efficacy of pd-1 inhibitors in relapsed/refractory classic hodgkin lymphoma: checkpoint molecules landscape and macrophage populations |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/0435aea250c1445fb445bd9fce6f207d |
| work_keys_str_mv |
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