Expression of PD-1 and PD-L1 increase in consecutive biopsies in patients with classical Hodgkin lymphoma

Hollander, Peter; Amini, Rose‐Marie; Ginman, Beatrice; Molin, Daniël; Enblad, Gunilla; Glimelius, Ingrid

doi:10.1371/journal.pone.0204870

Cited by 27 publications

(22 citation statements)

References 33 publications

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“…PD1 and PD-L1 are both therapeutic targets and biomarker of outcome [25]. A recent publication found increasing levels of PD1-positive T cells in cHL at relapse after conventional chemotherapy [26]. We were not able to confirm these results.…”

Section: Discussionmentioning

confidence: 56%

Therapeutic targets and microenvironment in sequential biopsies of classical Hodgkin lymphoma at diagnosis and relapse

et al. 2019

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Classical Hodgkin lymphoma is dominated by the non-neoplastic microenvironment, while the neoplastic Hodgkin-Reed-Sternberg cells compose only a minority of cells in the lymphoma tissue. Both the Hodgkin-Reed-Sternberg cells due to their expression of CD30 and PD-L1 and the microenvironment with abundant T cells and expression of PD1 are specifically targeted by new treatment concepts. We aimed to understand the dynamics of therapeutic targets in patients treated with conventional chemotherapy. We analyzed sequential biopsy specimens obtained at diagnosis and at relapse from the same patient for morphology, immunophenotype, and microenvironmental components. The morphological subtype changed between primary and relapse biopsy in 20% of cases. The immunophenotype was stable with respect to CD30, CD3, and LMP1 but variable with respect to CD15 and CD20 expression. Gene expression revealed 8 upregulated and 20 downregulated genes at relapse (p ≤ 0.05) with a consistent logarithmic fold change direction in at least 75% of all cases. For PD1, we found discrepant results between gene expression analysis (decrease at relapse) and number of PD1-positive cells assessed by immunohistochemistry (unchanged at relapse). PD-L1 in the neoplastic cells appeared unchanged between primary diagnosis and relapse. The expression of the therapeutic targets CD30, PD1, and PD-L1 can reliably be assessed in tumor specimen at first diagnosis and is unchanged under conventional chemotherapy.

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Section: Discussionmentioning

confidence: 56%

Therapeutic targets and microenvironment in sequential biopsies of classical Hodgkin lymphoma at diagnosis and relapse

et al. 2019

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“…To our interest, Hollander et al . recently reported the decreased expression of PD‐L1 in HRS cells in consecutive biopsies of a small subset (10–18%) in CHL cases despite their treated or untreated setting, but unfortunately without any reference to their histopathological findings, A downregulation of PD‐L1 on HRS cells might include several mechanisms, such as genetic alterations and epigenetic regulation .…”

Section: Discussionmentioning

confidence: 96%

Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry

Kohno

Sakakibara

Iwakoshi

et al. 2020

Pathology International

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Although several reports have highlighted neoplastic PD‐L1 (nPD‐L1) expression in classic Hodgkin lymphoma (CHL), some have addressed associations between its expression and detailed histopathologic features. Here we describe four cases of syncytial variant of CHL (SV‐CHL), with and without Epstein–Barr virus (EBV) association, and highlight the diagnostic utility of PD‐L1 (clone SP142) immunohistochemistry. The patients were a 61‐year‐old male, 45‐year‐old male, 85‐year‐old female, and 89‐year‐old female. All presented with cervical or axillary lymphadenopathy, which on biopsy had the established histopathologic features of SV‐CHL with a biphasic pattern of cohesive sheets of large tumor cells and typically scattered distribution of Hodgkin and Reed–Stenberg (HRS) cells. These tumor cells showed identical immunophenotypic findings for CD15, CD30, Fascin, PAX5, OCT2, BOB1 and EBV harboring, regardless of location. The exception was absent or decreased expression of nPD‐L1 from tumor cells in the confluent sheets, contrasting with HRS cell positivity in typical areas of CHL. These findings offer the first suggestion of possible downregulation of nPD‐L1 expression in association with the histopathologic progression of CHL. The results may be relevant for recognizing ‘confluent’ sheets in the diagnostic workup for SV‐CHL.

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“…In several tumor types, especially CHL and other tumors with a marked inflammatory infiltrate, a major component of PD-L1 expression within the total cellularity is supposed to derive from tumor-infiltrating macrophages [ 9 , 33 , 35 ]. Thus, in addition to the CD68 and CD163 expression, the number of PD-L1-positive cells in formalin-fixed paraffin-embedded tissue can be considered as an adverse prognostic factor for elderly patients with HL [ 9 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

An Autopsy Case of an Elderly Patient with Classic Hodgkin Lymphoma Presenting with a Plethora of Clinical Symptoms and Signs

et al. 2020

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Patient: Female, 88-year-old Final Diagnosis: Hodgkin lymphoma Symptoms: Fever • weight loss • dypnea Medication: — Clinical Procedure: — Specialty: Pathology Objective: Unusual clinical course Background: Hodgkin lymphoma (HL) is a potentially curable disease with favorable outcomes. However, elderly patients with HL usually have more adverse prognostic factors and hence a much worse prognosis than younger patients. Case Report: The patient was a woman in her 80s. She reported high fever, anorexia, and a weight loss of 8 kg within 5 months. She had been on treatment for diabetes mellitus and hypertension. She had undergone percutaneous coronary intervention and pacemaker implantation to treat acute coronary syndrome and sinus arrhythmia, respectively. Blood tests showed elevation of alkaline phosphatase, C-reactive protein, leukocyte count, CA 19-9, and carcinoembryonic antigen. Computed tomography did not show tumors in the liver, and cholangitis and sepsis were suspected. Aspartate transaminase, alanine aminotransferase, and total bilirubin gradually increased through the course of the patient’s hospital stay. Despite treatment, her condition deteriorated and she died 22 days after hospital admission. At autopsy, we found stage IV HL with lymph node swelling on both sides of the diaphragm, as well as diffusely disseminated nodules in the liver and spleen. Conclusions: Our patient had several poor prognostic factors including B symptoms, comorbidity, advanced stage, Epstein-Barr virus infection, and expression of programmed death-ligand 1 and interleukin-6, all of which were closely connected with her advanced age. Her age and comorbidities may have been the most adverse prognostic factors for her illness. An effective HL screening method for elderly individuals should be developed to ameliorate poor prognosis and adverse outcomes.

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Expression of PD-1 and PD-L1 increase in consecutive biopsies in patients with classical Hodgkin lymphoma

Cited by 27 publications

References 33 publications

Therapeutic targets and microenvironment in sequential biopsies of classical Hodgkin lymphoma at diagnosis and relapse

Therapeutic targets and microenvironment in sequential biopsies of classical Hodgkin lymphoma at diagnosis and relapse

Syncytial variant of classic Hodgkin lymphoma: Four cases diagnosed with the aid of CD274/programmed cell death ligand 1 immunohistochemistry

An Autopsy Case of an Elderly Patient with Classic Hodgkin Lymphoma Presenting with a Plethora of Clinical Symptoms and Signs

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