Programmed cell death protein1 (PD1)-expression in the microenvironment of classical Hodgkin lymphoma at relapse after conventional chemotherapy and at relapse on anti-PD1 treatment

Sasse, Stephanie; Reddemann, Katharina; Diepstra, Arjan; Borchmann, Sven; Oschlies, Ilske; Schnitter, Antje; Engert, Andreas; Borchmann, Peter; Klapper, Wolfram

doi:10.3324/haematol.2018.207829

Cited by 4 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we demonstrated that LR-CHL shows a clearly distinct PD-1/PD-L1 profile when compared to other CHL subtypes, including more PD-1 + T cells and fewer PD-L1 genetic alterations in HRS cells. This is consistent with results from previous small case series in LR-CHL ( 41 , 42 ). The response of PD-1 blockade by pathological subtype in CHL has not been reported, and further evaluation is warranted.…”

Section: Discussionsupporting

confidence: 93%

Single-cell profiling reveals the importance of CXCL13/CXCR5 axis biology in lymphocyte-rich classic Hodgkin lymphoma

Aoki

Chong

Takata

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Lymphocyte-rich classic Hodgkin lymphoma (LR-CHL) is a rare subtype of Hodgkin lymphoma. Recent technical advances have allowed for the characterization of specific cross-talk mechanisms between malignant Hodgkin Reed-Sternberg (HRS) cells and different normal immune cells in the tumor microenvironment (TME) of CHL. However, the TME of LR-CHL has not yet been characterized at single-cell resolution. Here, using single-cell RNA sequencing (scRNA-seq), we examined the immune cell profile of 8 cell suspension samples of LR-CHL in comparison to 20 samples of the mixed cellularity (MC, 9 cases) and nodular sclerosis (NS, 11 cases) subtypes of CHL, as well as 5 reactive lymph node controls. We also performed multicolor immunofluorescence (MC-IF) on tissue microarrays from the same patients and an independent validation cohort of 31 pretreatment LR-CHL samples. ScRNA-seq analysis identified a unique CD4+ helper T cell subset in LR-CHL characterized by high expression of Chemokine C-X-C motif ligand 13 (CXCL13) and PD-1. PD-1+CXCL13+ T cells were significantly enriched in LR-CHL compared to other CHL subtypes, and spatial analyses revealed that in 46% of the LR-CHL cases these cells formed rosettes surrounding HRS cells. MC-IF analysis revealed CXCR5+ normal B cells in close proximity to CXCL13+ T cells at significantly higher levels in LR-CHL. Moreover, the abundance of PD-1+CXCL13+ T cells in the TME was significantly associated with shorter progression-free survival in LR-CHL (P = 0.032). Taken together, our findings strongly suggest the pathogenic importance of the CXCL13/CXCR5 axis and PD-1+CXCL13+ T cells as a treatment target in LR-CHL.

show abstract

Section: Discussionsupporting

confidence: 93%

Single-cell profiling reveals the importance of CXCL13/CXCR5 axis biology in lymphocyte-rich classic Hodgkin lymphoma

Aoki

Chong

Takata

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…This is in contrast to what was reported by Roemer et al, 4 who detected amplification of the 2 genes in 39 of 108 CHL and copy gain of chromosome 9p24.1 in 61 additional CHL. However, Sasse et al, 5 more recently reported results similar to ours. In fact, such discrepancy may be due to technical reasons, as we used a commercial CE-IVD-approved specific probe, whereas a home-made probe was used by Roemer et al, 4 who, additionally, provided a questionable definition for amplification in their paper.…”

supporting

confidence: 88%

PD-1 and PD-L1 Immunohistochemistry as a Diagnostic Tool for Classic Hodgkin Lymphoma in Small-volume Biopsies

Uccella

Magnoli²,

Vivian

et al. 2021

American Journal of Surgical Pathology

View full text Add to dashboard Cite

“…This result was consistent with the results of Sasse and al. [10], who found that in the tumor microenvironment of cHL, patients relapsed after anti-PD-1; PD-1 were decreased but remained positively expressed on T cell surfaces at a level easily detectable by immunohistochemistry. In our study with fresh cells analysis, we did not find changes of PD-1 staining on the CD4+ T lymphocytes of tumor microenvironment, whether patients were exposed or naïve to anti-PD-1.…”

Section: Discussionmentioning

confidence: 99%

“…Sasse and al. reported a patient case series that illustrated that, at relapse after anti-PD-1, the target PD-1 was present on T-cells in the vicinity of Reed Sternerg cells, at a level easily detectable by immunohistochemistry [10]. The Sasse and al.…”

Section: Introductionmentioning

confidence: 98%

CD8+ T Lymphocytes Immune Depletion and LAG-3 Overexpression in Hodgkin Lymphoma Tumor Microenvironment Exposed to Anti-PD-1 Immunotherapy

Michot

Mouraud

Adam

et al. 2021

Cancers

View full text Add to dashboard Cite

Background: Resistance to anti-PD-1 remains a considerable clinical challenge for the treatment of patients with classical Hodgkin lymphoma (cHL), and mechanisms of anti-PD-1 resistance remain unknown. This pilot study aims to investigate the tumor microenvironment in patients with cHL relapsing after anti-PD-1. Methods: This study investigated tumor samples of eight patients with cHL, including four patients exposed to anti-PD-1 with a paired longitudinal histological analysis before and after anti-PD-1, and four patients not exposed to anti-PD-1 who served as control for the cellular biological investigations. Fresh cells tumor microenvironment analysis included phenotypic characterization of their T cell surfaces immune checkpoint markers PD-1, PD-L1, ICOS, TIM-3, LAG-3, 41-BB and BTLA. Tumor tissues immunohistochemistry staining included CD30, CD4, CD8, CD68, CD163, PD-L1, PD-1, LAG-3 and TIM-3. Findings: Paired longitudinal tumor tissues analysis in the tumor microenvironment found a CD8+ lymphocytes tumor depletion and an increase of LAG-3 staining after anti-PD-1 exposure. The fresh cells analysis of the tumor microenvironment in patients exposed to anti-PD-1 found CD8+ lymphocyte depletion, with an elevated CD4+/CD8+ lymphocytes ratio (median ratio 9.77 in exposed anti-PD-1 versus 2.39 in not-exposed anti-PD-1 patients; p = 0.0943). On the cell surfaces of CD4+ lymphocytes, the median positive expression of LAG-3 was significantly higher in the samples exposed to anti-PD-1 compared to the controls (15.05 [IQR:17.91–10.65] versus 3.84 [IQR 1.87–6.57]; p = 0.0376). Interpretation: This pilot study proposes hypotheses for understanding the resistance to immunotherapies in patients with Hodgkin lymphoma. Hodgkin lymphoma exposed to anti-PD-1 correlated in tumor microenvironment with an immune depletion of CD8+ T lymphocytes and overexpression of LAG-3 on CD4+ helper T lymphocytes.

show abstract

Programmed cell death protein1 (PD1)-expression in the microenvironment of classical Hodgkin lymphoma at relapse after conventional chemotherapy and at relapse on anti-PD1 treatment

Cited by 4 publications

References 5 publications

Single-cell profiling reveals the importance of CXCL13/CXCR5 axis biology in lymphocyte-rich classic Hodgkin lymphoma

Single-cell profiling reveals the importance of CXCL13/CXCR5 axis biology in lymphocyte-rich classic Hodgkin lymphoma

PD-1 and PD-L1 Immunohistochemistry as a Diagnostic Tool for Classic Hodgkin Lymphoma in Small-volume Biopsies

CD8+ T Lymphocytes Immune Depletion and LAG-3 Overexpression in Hodgkin Lymphoma Tumor Microenvironment Exposed to Anti-PD-1 Immunotherapy

Contact Info

Product

Resources

About