PD-L1 expression in peripheral T-cell lymphomas is not related to either <i>PD-L1</i> gene amplification or rearrangements

Manso, Rebeca; Rodríguez‐Perales, Sandra; Torres-Ruíz, Raúl; Santonja, Carlos; Rodríguez-Pinilla, Socorro-María

doi:10.1080/10428194.2021.1881511

Cited by 12 publications

(12 citation statements)

References 51 publications

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“…However, PD-L1 + tumour cells were frequently found in 34 of 45 ALK+ (76%) and 21 of 50 ALK− (42%) sALCL patients [20]. In addition, sALCL also showed less frequent expression of TFH markers [26,27]. The results supported sALCL as a distinct disease from AITL and PTCL-NOS.…”

Section: Discussionmentioning

confidence: 90%

Large tumour cell group, combinations of CMYC+ or PD-1+ tumour cells and intense PD-L1+ cell reaction are important prognostic factors in nodal T-cell lymphomas with T follicular helper markers

Mihashi

Kimura

Iwasaki

et al. 2021

Preprint

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Background The clinicopathological characteristics and prognostic factors in nodal T-cell lymphomas with T follicular helper markers (TFH+) are not adequately investigated. Methods Immunohistologically, we selected 22 patients with TFH + lymphoma in 47 of peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH + lymphomas. Results Thirteen large cell and nine small cell PTCL patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell TFH + PTCL showed CMYC expression in 10 patients (76.9%), and four of 11 large cell group (36.4%) had somatic RHOA G17V gene mutation by Sanger sequencing. In TFH + lymphomas, large cell TFH + PTCL patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). CMYC + tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1 + non-neoplastic cells (high PD-L1 + cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC + or PD-1 + tumour cells and high PD-L1 + cell group indicated significantly poor prognosis (p < 0.01). Conclusion Large cell TFH + PTCL indicated poor prognosis in TFH + lymphomas. These data suggested that CMYC + tumour cells and intense PD-L1 + cell reaction influenced tumour cell progression in TFH + lymphomas, and PD-1 + tumour cell/intense PD-L1 + cell reactions may play a role in immune evasion.

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Section: Discussionmentioning

confidence: 90%

Large tumour cell group, combinations of CMYC+ or PD-1+ tumour cells and intense PD-L1+ cell reaction are important prognostic factors in nodal T-cell lymphomas with T follicular helper markers

Mihashi

Kimura

Iwasaki

et al. 2021

Preprint

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“…However, PD-L1+ tumour cells were frequently found in 34 of 45 ALK+ (76%) and 21 of 50 ALK− (42%) sALCL patients [ 19 ]. In addition, sALCL also showed less frequent expression of TFH markers [ 26 , 27 ]. The results supported sALCL as a distinct disease from AITL and PTCL-NOS.…”

Section: Discussionmentioning

confidence: 99%

Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers

et al. 2021

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Background The clinicopathological characteristics and prognostic factors in nodal peripheral T-cell lymphomas (PTCLs) with two or more T follicular helper markers (TFH+) are not adequately investigated. Methods Immunohistologically, we selected 22 patients with TFH+ lymphoma (PTCL-TFH) in 47 of PTCL-not otherwise specified (NOS), and subclassified into large and small cell groups. We compared the two groups with 39 angioimmunoblastic T-cell lymphoma (AITL) and seven follicular T-cell lymphoma (F-TCL) patients. Prognostic factors were analysed by overall survival in patients with three types of TFH+ PTCLs. Results Thirteen large cell and nine small cell PTCL-TFH patients had more than two TFH markers including programmed cell death-1 (PD-1). Large cell PTCL-TFH showed frequent CMYC expression in 10 patients (77%), and four of 11 large cell group (36%) had somatic RHOA G17V gene mutation by Sanger sequencing. Large cell PTCL-TFH patients showed significantly worse prognosis than those of the small cell group, AITL, and F-TCL (p < 0.05). In TFH+ PTCLs, CMYC+ tumour cells, and combined PD-1 ligand 1 (PD-L1) + tumour cells and intense reaction of PD-L1+ non-neoplastic cells (high PD-L1+ cell group) were significantly poor prognostic factors (p < 0.05). Combinations of CMYC+ or PD-1+ tumour cells and high PD-L1+ cell group indicated significantly poor prognosis (p < 0.01). Conclusion Large cell PTCL-TFH indicated poor prognosis in TFH+ PTCLs. These data suggested that CMYC+ tumour cells and intense PD-L1+ cell reaction influenced tumour cell progression in TFH+ PTCLs, and PD-1+ tumour cell/intense PD-L1+ cell reactions may play a role in immune evasion.

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“…The high expression of PD-1 in AITL was confirmed as early as 2007 ( Shimauchi et al, 2007 ), and subsequent studies also found an increased number of PD-1-expressing cells in 93% of AITLs and 62% of follicles outside PTCL-NOS, leading to an immunosuppressive microenvironment ( Krishnan et al, 2010 ). In a series of studies over recent years, Manso et al (2021) evaluated PD-1 expression in 168 PTCL subtypes via immunohistochemistry using a cutoff value of 10% and reported that PD-1 was expressed in 61.6% (52/86) of AITL, 39.3% (22/56) of PTCL-NOS, and 13.3% (2/15) of ALK− ALCL cases. In contrast, PD-1 positivity was barely detectable in ALK+ ALCL.…”

Section: Pd-1/pd-l Expression In Peripheral T-cell Lymphomamentioning

confidence: 99%

Immune Checkpoint Inhibitors in Peripheral T-Cell Lymphoma

Chen

Wei

et al. 2022

Front. Pharmacol.

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Peripheral T-cell lymphomas (PTCLs) are highly heterogeneous and present significant treatment challenges. Immune checkpoint therapies, such as PD-1 and CTLA-4 inhibitors, have significantly changed the clinical management paradigm of tumors. The roles of immune checkpoints in PTCL and related agents have been actively explored over recent years. PD-1 and PD-L1 expression is detectable in both PTCL and immune cells within the tumor microenvironment and forms the basis for the exploration of antibodies targeting these proteins. Such antibodies are currently being investigated in clinical trials to guide individualized therapy. PD-1/PD-L1 inhibitors alone and in combination with chemotherapy, radiotherapy, or targeted therapy have shown broad clinical efficacy and improved the survival of cancer patients. Studies of other immune checkpoint proteins, such as CTLA-4, TIM-3, LAG-3, and TIGIT, are likely to provide potential novel targets for immunotherapy. Here, we review the role of and recent advances in immune checkpoint blockade in common subtypes of PTCL, focusing on the anti-tumor immune responses to PD-1/PD-L1 blockers.

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PD-L1 expression in peripheral T-cell lymphomas is not related to either PD-L1 gene amplification or rearrangements

Cited by 12 publications

References 51 publications

Large tumour cell group, combinations of CMYC+ or PD-1+ tumour cells and intense PD-L1+ cell reaction are important prognostic factors in nodal T-cell lymphomas with T follicular helper markers

Large tumour cell group, combinations of CMYC+ or PD-1+ tumour cells and intense PD-L1+ cell reaction are important prognostic factors in nodal T-cell lymphomas with T follicular helper markers

Large cell morphology, CMYC+ tumour cells, and PD-1+ tumour cell/intense PD-L1+ cell reactions are important prognostic factors in nodal peripheral T-cell lymphomas with T follicular helper markers

Immune Checkpoint Inhibitors in Peripheral T-Cell Lymphoma

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