Expression pattern of <scp>PD</scp>‐L1 and <scp>PD</scp>‐L2 in classical Hodgkin lymphoma, primary mediastinal large B‐cell lymphoma, and gray zone lymphoma

Tanaka, Yosuke; Maeshima, Akiko Miyagi; Nomoto, Junko; Makita, Shinichi; Fukuhara, Suguru; Munakata, Wataru; Maruyama, Dai; Tobinai, Kensei; Kobayashi, Yasuhito

doi:10.1111/ejh.13033

Cited by 44 publications

(35 citation statements)

References 32 publications

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“…To our knowledge, this is the first study to report neoplastic expression of PD‐L1, and its correlation with pathological findings (i.e., anatomical position), in two cases of mediastinal composite lymphoma of NSCHL and PMBL. Several authors recently reported PD‐L1 expression on neoplastic cells in NSCHL, PMBL and MGZL; generally finding that the positive percentages were highest in NSCHL, lowest in PMBL, and intermediate in MGZL . Accordingly, in our control series, nPD‐L1 expression was observed in 100% of NSCHL (n = 7) and 18% of PMBL (n = 11).…”

Section: Discussionsupporting

confidence: 62%

“…Investigation of various markers have resulted in few consensus panels . Notably, CD274/programmed cell death ligand 1 (PD‐L1) positivity on tumor cells is characteristic of CHL, and is less frequently exhibited by PMBL . This suggests that PMBL may be divided into PD‐L1‐positive and ‐negative subgroups that are not yet well‐defined.…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic utility of programmed cell death ligand 1 (clone SP142) in mediastinal composite lymphoma: A report of two cases

Sakakibara

Kohno

Iwakoshi

et al. 2020

Pathology International

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Composite lymphoma is a well‐known diagnostic entity exhibiting the synchronous occurrence of two or more distinct types of lymphomas in the same specimen. Here we report two patients, a 14‐year‐old female (Case 1) and a 45‐year‐old male (Case 2), with mediastinal composite lymphoma, comprising nodular sclerosis classic Hodgkin lymphoma (NSCHL) and primary mediastinal large B‐cell lymphoma (PMBL). Both patients had a mediastinal mass, and manifested two different histologic components in the same biopsy, one characteristic of NSCHL and the other PMBL. The NSCHL areas included Hodgkin and Reed–Sternberg (HRS) cells with typical immunophenotypic features (CD30‐positive and CD20‐negative), whereas the sheets of large tumor cells characteristic of PMBL were strongly and uniformly CD20‐positive. Interestingly, although both cases showed neoplastic PD‐L1 (nPD‐L1) positivity on the HRS cells of NSCHL, they differed regarding nPD‐L1 expression on the PMBL tumor cells. In Case 1, the nPD‐L1‐negative PMBL component was anatomically situated outside the NSCHL lesion. On the other hand, in Case 2, the nPD‐L1‐positive PMBL component was characterized by transitional or continuous areas with the NSCHL component. These findings suggested that nPD‐L1 expression may define two subtypes of PMBL that are more similar to or distinct from classic Hodgkin lymphoma.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Diagnostic utility of programmed cell death ligand 1 (clone SP142) in mediastinal composite lymphoma: A report of two cases

Sakakibara

Kohno

Iwakoshi

et al. 2020

Pathology International

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“…PD‐L2 expression was even present in some cases with missing PD‐L1 expression . In other malignancies such as primary mediastinal large B‐cell lymphoma and colorectal cancer, an increase in PD‐L2 expression and a negative prognostic value was also shown. This outlines the potential relevance of PD‐L2 expression as inhibitory immune checkpoint.…”

Section: Discussionmentioning

confidence: 96%

Prognostic significance of PD‐L2 expression in patients with oral squamous cell carcinoma—A comparison to the PD‐L1 expression profile

et al. 2019

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Background Despite the observed association of increased PD‐L1 expression in peripheral blood of oral squamous cell carcinoma (OSCC) patients with histomorphologic parameters, the role of the PD1 ligands—PD‐L1 and PD‐L2—is insufficiently understood. Aim of the study was to investigate whether the alterations of PD‐L1 and PD‐L2 expression in blood are associated with survival and could serve as immune monitoring parameter. Moreover, it should be analyzed if PD‐L2 is differentially expressed in tissue and blood samples of OSCC patients compared to healthy controls and if there is an association of PD‐L2 expression with histomorphologic and prognostic tumor parameters. Methods PD‐L2 mRNA expression was analyzed in tumors and healthy oral mucosa specimens and in corresponding peripheral blood samples of 48 OSCC patients and 26 healthy controls using RT‐qPCR. A cutoff point (COP) was determined and a chi‐square test (χ2 test) was carried out. Survival analysis of PD‐L2 and previously reported PD‐L1 expression data was performed using Kaplan‐Meier analysis (Log‐rank test). Results PD‐L2 expression in tissue samples was significantly (P < 0.001) higher in OSCC patients compared to healthy controls. A significant association of PD‐L2 expression above the COP (positive) with malignancy was ascertained (P < 0.001). A significant (P = 0.01) association of previously reported PD‐L1 expression rates in peripheral blood with survival could be shown. Conclusion Peripheral blood PD‐L1 expression might be a prognostic marker for OSCC patients and a possible parameter to monitor immune dysfunction in malign diseases. In the peripheral blood, PD‐L1 might be more relevant for immune tolerance than PD‐L2. Local PD‐L2 expression in tissue samples might be useful as a diagnostic parameter for malignancy and could contribute to the immunosuppressive local microenvironment in OSCC.

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“…The same is true for lymphomas. [106][107][108][109][110][111] Development of multiple myeloma is also supported by essentially the same cell logistics, [112][113][114][115][116][117] and this seems to apply to sarcomas too. [118][119][120][121][122][123] The shared group of functional properties at issue here is in fact a subset of the currently recognized hallmarks of cancer.…”

Section: Related Specific Regulationmentioning

confidence: 97%

<p>Plausibility of trophoblastic-like regulation of cancer tissue</p>

Piechowski¹

2019

CMAR

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Background: Thus far, a well-established logical pattern of malignancy does not exist. The current approach to cancer properties is primarily descriptive with usually, for each of them, extensive analyses of the underlying associated biomolecular mechanisms. However, this remains a catalog and it would be valuable to determine the organizational chart that could account for their implementation, hierarchical links and input into tumor regulation. Hypothesis: Striking phenotypic similarities exist between trophoblast (invasive and expanding early placenta) and cancer regarding cell functions, logistics of development, means of protection and capacity to hold sway over the host organism. The concept of cancer cell trophoblastic-like transdifferentiation appears to be a rational proposal in an attempt to explain this analogy and provide a consistent insight into how cancer cells are functioning. Should this concept be validated, it could pave the way to promising research and therapeutic perspectives given that the trophoblastic properties are vital for the tumor while they are permanently epigenetically turned off in normal cells. Specifically targeting expression of the trophoblastic master genes could thereby be envisaged to jeopardize the tumor and its metastases without, in principle, inducing adverse side effects in the healthy tissues. Conclusion: A wide set of functional features of cancer tissue regulation, including some apparently paradoxical facts, was reviewed. Cancer cell misuse of physiological trophoblastic functions can clearly account for them, which identifies trophoblastic-like transdifferentiation as a likely key component of malignancy and makes it a potential relevant anticancer target.

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Expression pattern of PD‐L1 and PD‐L2 in classical Hodgkin lymphoma, primary mediastinal large B‐cell lymphoma, and gray zone lymphoma

Abstract: We identified increased staining of PD-L1 in cHL and that of PD-L2 in PMBL. GZL had a pattern similar to that of cHL.

Cited by 44 publications

References 32 publications

Diagnostic utility of programmed cell death ligand 1 (clone SP142) in mediastinal composite lymphoma: A report of two cases

Diagnostic utility of programmed cell death ligand 1 (clone SP142) in mediastinal composite lymphoma: A report of two cases

Prognostic significance of PD‐L2 expression in patients with oral squamous cell carcinoma—A comparison to the PD‐L1 expression profile

<p>Plausibility of trophoblastic-like regulation of cancer tissue</p>

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