PD-1 and PD-L1 expression in bone and soft tissue sarcomas

Torabi, Alireza; Amaya, Clarissa; Wians, Frank H.; Bryan, Brad Allen

doi:10.1016/j.pathol.2017.05.003

Cited by 64 publications

(56 citation statements)

References 35 publications

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“…Several studies have been undertaken to evaluate the immune landscape in patients with STS. Programmed cell death‐1 was overexpressed in osteosarcoma, chondrosarcoma, all variants of liposarcoma, and rhabdomyosarcoma, whereas PD‐L1 expression was relatively rare . Another 2 studies on well‐/dedifferentiated liposarcoma (WDLPS/DDLPS) described composition and distribution of the tumor‐infiltrating lymphocytes (TILs) in inflammatory WDLPS and suggested that PD‐1 was expressed in 65% patients, which provided limited clues for the immune landscape in RLPS due to the relatively small sample size .…”

Section: Introductionmentioning

confidence: 99%

“…Programmed cell death-1 was overexpressed in osteosarcoma, chondrosarcoma, all variants of liposarcoma, and rhabdomyosarcoma, whereas PD-L1 expression was relatively rare. 28 Another 2 studies on well-/dedifferentiated liposarcoma (WDLPS/DDLPS) described composition and distribution of the tumor-infiltrating lymphocytes (TILs) in inflammatory WDLPS and suggested that PD-1 was expressed in 65% patients, which provided limited clues for the immune landscape in RLPS due to the relatively small sample size. 29,30 Pollack et al 31 characterized the TCR repertoires of infiltrating lymphocytes in STSs, and the results suggested that undifferentiated pleomorphic sarcoma was supposed to be a potential subtype that might respond effectively to immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive immune characterization and T‐cell receptor repertoire heterogeneity of retroperitoneal liposarcoma

et al. 2019

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Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas and lacks effective treatment. This study aimed to provide a thorough profile of immune characteristics of RLPS. This study included 56 RLPS patients. Multisite tumor tissues were collected from 16 patients. Immunohistochemistry was carried out to identify CD4+, CD8+, FoxP3+, CD20+, or programmed cell death‐1 (PD‐1)+ tumor infiltrating lymphocytes (TILs) and Programmed cell death ligand‐1 (PD‐L1) expression in tumor tissues. Ultradeep sequencing of T‐cell receptor (TCR) β‐chain gene was carried out in 42 tumor samples as well as peripheral blood samples collected from 6 patients. In RLPS, TILs were distributed in 3 patterns and T cells were more prevalent than B cells. Generally, the proportion of TILs decreased and PD‐L1 expression increased with tumor progression. Patients with higher PD‐1/PD‐L1 expression tended to have poorer prognosis, whereas patients with tertiary lymphoid structure tended to have a favorable disease‐free survival. Although T‐cell clones in tumors were quite different from those in peripheral blood, TCR sequencing showed low TCR repertoire reads as well as polyclonal status within tumors, which indicated limited T cell response in the tumors. Both TILs distribution and TCR repertoires suggested spatial immune heterogeneity in RLPS. Our research described the immune landscape of RLPS, and suggested RLPS might be a kind of tumor with low T cell infiltration as well as great immune heterogeneity. Therefore, strategies that can facilitate lymphocytic infiltration and immune reactivity need to be developed in the future to improve the efficacy of immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive immune characterization and T‐cell receptor repertoire heterogeneity of retroperitoneal liposarcoma

et al. 2019

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“…>2+ and >5% (12)). In some of these series, the frequency of PD-L1 expression ranges from absent (0%) with the Abcam (ab58810 and ab205921) and SP142 clones (7,8) to low (12%: H-130 clone)(9), intermediate (26-30%: AM2653AF-N. Acris & SP263)(10, 11) and high (58% & 65% with BD Pharmingen and R&D Systems and the H-130, Santa Cruz clones, respectively (12,13)). Although strong correlation has been established for some clones (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…The frequency of PD-L1 expression in sarcomas reported in the literature is highly variable with incidences ranging from 0% to 65% (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). In their analysis, some of these series have combined statistical analysis of the two molecularly characteristic groups of sarcomas, that is those associated with recurrent specific genetic events (e.g.…”

Section: Introductionmentioning

confidence: 99%

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PD-L1 expression in 522 selected sarcomas with subset analysis of recurrent or metastatic matched samples and association with tumour-infiltrating lymphocytes

Vargas

Maclean

Sioson

et al. 2019

Preprint

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We assessed the frequency of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in a cohort of 522 sarcomas from 457 patients, incuding a subset of 46 patients with 63 matched samples from local recurrence or metastases with primary tumours and/or metachronous metastases. We also investigated the correlation of PD-L1 with the presence and degree of tumour-infiltrating lymphocytes (TILs) in a subset of cases. IHC was performed using the PD-L1 SP263 companion kit (VENTANA) on tissue microarrays from an archival cohort. Evaluation of PD-L1 and TILs was performed on full sections for a subset of 23 cases. Fisher's exact and Mann Whitney test were used to establish significance (P <0.05). PD-L1 positive expression (≥1%) was identified in 31% of undifferentiated pleomorphic sarcomas, 29% of angiosarcomas, 26% of rhabdomyosarcomas, 18% of myxofibrosarcomas, 11% of leiomyosarcomas and 10% of dedifferentiated liposarcomas. Negative expression was present in all atypical lipomatous tumous/well-differentiated lipoasarcomas, myxoid liposarcomas, synovial sarcomas, pleomorphic liposarcomas, and Ewing sarcomas. PD-L1 IHC was concordant in 81% (38 of 47) of matched/paired samples. PD-L1 IHC was discordant in 19% (9 of 47 matched/paired samples), displaying differences in the proportion of cells expressing PD-L1 amongst pairedsamples with the percentage of PD-L1-positive cells increasing in the metastatic/recurrent site compared to the primary in 6 of 9 cases (67%). Significant correlation between PD-L1 expression and the degree of TILs was exclusively identified in the general cohort of leiomyosarcomas, but not in other sarcoma subtypes or in metastatic/recurrent samples. We conclude that the prevalence of PD-L1 expression in selected sarcomas is variable and likely to be clone dependent.Importantly, we demonstrated that PD-L1 can objectively increase in a small proportion of metastases/recurrent sarcomas, offering the potential of treatment benefit to immune checkpoint inhibitors in this metastatic setting.

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