<scp>PD</scp>1 and <scp>PDL</scp>1 expression in primary central nervous system diffuse large B‐cell lymphoma are frequent and expression of <scp>PD</scp>1 predicts poor survival

Four, Marion; Cacheux, Valère; Tempier, Ariane; Platero, Dolorès; Fabbro, Michel; Marin, Grégory; Leventoux, Nicolas; Rigau, Valérie; Costes-Martineau, Valérie; Szablewski, Vanessa

doi:10.1002/hon.2375

Cited by 51 publications

(37 citation statements)

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“…In previous studies of PCNS-DLBCL, high PD-L1 expression was unrelated, 21 or related to a favorable prognosis; 20,22 an increased PD-1 + TILs were related to an unfavorable prognosis. 20,21 This study included the largest population of any similar work to date, analyzed the prognostic implications in experimental and validation groups and according to treatment modality, involved a multivariate analysis, quantified PD-L1 expression and enumerated TILs, and evaluated PD-L1 expression together with CD8 + or PD-1 + TILs. We found that tumoral PD-L1 expression was an independent prognostic indicator of a poor OS.…”

Section: Pd-1 Expression Is Induced By T-cell Receptor Signaling On Amentioning

confidence: 82%

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High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

et al. 2019

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We investigated the clinicopathological role of the PD-1/PD-L1 pathway in primary diffuse large B-cell lymphoma of the central nervous system (PCNS-DLBCL) arising in the immune-privileged site. PD-L1 immunostaining of ≥30% of tumor cells was defined as tPD-L1+, and PD-L1 immunostaining of ≥30% of total cellularity, including tumor and non-tumoral cells, as tmPD-L1+ . PD-1 + and CD8 + tumor-infiltrating lymphocytes (TILs) were enumerated. Thirty-five cases (35.7%) were tPD-L1+ and 47 cases (48%) were tmPD-L1+ . The number of TILs was greater in tmPD-L1+ cases than in tmPD-L1− cases (CD8 + , P= .050; PD-1 + , P= .019). tPD-L1+ and tmPD-L1+ cases tended to have a poor performance status. In contrast, the numbers of CD8 + and PD-1 + TILs tended to be higher in patients with a good performance status and MYC/BCL2 negativity. Patients with tPD-L1+ had a worse overall survival (P= .026), and those with increased CD8 + or PD-1 + TILs tended to have a better overall survival (P= .081 and 0.044, respectively). Tumoral PD-L1 expression and the number of PD-1 + TILs were independent prognostic factors. tPD-L1+ patients with a small number of CD8 + or PD-1 + TILs had the worst prognosis, and tPD-L1− patients with a large number of CD8 + or PD-1 + TILs had the best prognosis. In validation group, increased CD8 + or PD-1 + TILs were significantly associated with a prolonged survival, but PD-L1 had no prognostic significance. In conclusion, PD-L1 is frequently expressed in tumor cells and the immune microenvironment of PCNS-DLBCL and is correlated with increased TILs. PD-L1 and CD8 + and PD-1 + TILs have potential as prognostic biomarkers and therapeutic targets in PCNS-DLBCL. ARTICLE HISTORY

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Section: Pd-1 Expression Is Induced By T-cell Receptor Signaling On Amentioning

confidence: 82%

“…The few previous studies to address this issue used small sample numbers and yielded conflicting results. [19][20][21][22] Thus, we investigated PD-L1 expression and the numbers of CD8 + or PD-1 + TILs in tumor cells and the immune microenvironment of PCNS-DLBCL and analyzed their clinicopathological and prognostic implications.…”

Section: Introductionmentioning

confidence: 99%

High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

et al. 2019

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“…Interpretation of responses in some of these patients perhaps should be made with some caution, however, given the fact that 2 received whole-brain or focal irradiation immediately prior to nivolumab. 35 Nevertheless, these promising data, plus evidence that increased PDL-1/PD-1 expression in PCNSL may be associated with adverse prognosis, 36 constitute the basis for a multicenter phase 2 study of nivolumab in recurrent refractory PCNSL and PTL (NCT02857426).…”

Section: The Potential Of Novel Agents In Cns Lymphomasmentioning

confidence: 99%

Biology of CNS lymphoma and the potential of novel agents

Rubenstein

2017

Hematology

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Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease. A body of genetic evidence strongly suggested that primary CNS lymphomas (PCNSLs) are likely largely dependent on NF-κB prosurvival signals, with enrichment of mutations involving the B-cell receptor pathway, in particular myeloid differentiation primary response 88 and cluster of differentiation 79B. The first set of early-phase investigations that target NF-κB in PCNSL have now been completed and support the NF-κB hypothesis but at the same time reveal that much work needs to be done to translate these results into meaningful advances in survival for a large fraction of patients. Insights into secondary prosurvival pathways that mediate drug resistance is a priority for investigation. Similarly, further evaluation of the immune-suppressive mechanisms in the CNS lymphoma tumor microenvironment is requisite for progress. Combinatorial interventions that promote the antitumor immune response have significant potential. With increasing availability of targeted agents, there is also a need to develop more sensitive imaging tools, not only to detect this highly invasive brain neoplasm but also potentially to define an evolving molecular phenotype to facilitate precision medicine.

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“…1 Moreover, a recent report describes a higher incidence of neoplastic PD-L1 overexpression in primary DLBCL of the CNS (PCNS-DLBCL) compared to systemic ordinal cases. 12 This suggests that PD-L1 expression in tumor cells may play an important role in PCNS-DLBCL pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression

Sakakibara

Inagaki

Imaoka

et al. 2018

J Clin Exp Hematopathol

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Intravascular large B-cell lymphoma (IVLBCL) is a rare and clinically distinctive entity characterized by the almost exclusive growth of large cells within the lumen of blood vessels in particular capillaries. Reports of this peculiar disease, do not commonly address the PD-L1 expression on IVLBCL tumor cells. Here, we describe a 51-year-old Japanese woman who presented with rapidly progressive cognitive decline and higher brain dysfunction. CT scan and MRI revealed multiple ischemic foci in the cerebral hemispheres, ground-glass opacity in the lungs, and splenomegaly. Random skin biopsy for IVLBCL diagnosis yielded negative results. The patient experienced a rapidly deteriorating clinical course with no treatment, and died from the disease after 3 months of hospitalization. Post-mortem examination revealed systemic intravascular plugging of lymphoma cells, without mass lesions in the central nervous system or in visceral organs such as the lungs, liver, pituitary gland, ovaries, and uterus. The tumor cells were positive for CD10, CD20, BCL2, BCL6, and MUM1, but not other lineage-specific markers. Notably, the tumor cells showed strong PD-L1 expression. Our case was diagnosed as IVLBCL with neoplastic PD-L1 expression. These findings suggest that PD-L1 is associated with immune evasion of IVLBCL and may play a role in the pathogenesis and peculiar biological behavior of this unique disease. Additionally, PD-L1 may represent a possible therapeutic target for immune check-point inhibitors.

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PD1 and PDL1 expression in primary central nervous system diffuse large B‐cell lymphoma are frequent and expression of PD1 predicts poor survival

Cited by 51 publications

References 50 publications

High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

Biology of CNS lymphoma and the potential of novel agents

Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression

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PD1 and PDL1 expression in primary central nervous system diffuse large B‐cell lymphoma are frequent and expression of PD1 predicts poor survival

Cited by 51 publications

References 50 publications

High tumoral PD-L1 expression and low PD-1+ or CD8+ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

High tumoral PD-L1 expression and low PD-1+ or CD8+ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

Biology of CNS lymphoma and the potential of novel agents

Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression

Contact Info

Product

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High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system

High tumoral PD-L1 expression and low PD-1⁺ or CD8⁺ tumor-infiltrating lymphocytes are predictive of a poor prognosis in primary diffuse large B-cell lymphoma of the central nervous system