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(A) Magnetic resonance imaging depicting chondrosarcoma (CS) in the humerus (arrow) and (B) histology of high-grade CS stained with (C) SP142 and (D) SP263 assays at ×200 magnification showing a higher number of cells with PD-L1 immunoreactivity using the SP263 assay. (E) Clinical and tumor characteristics of the CS cohort.
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Immune checkpoint inhibitors (ICIs) such as PD1/PD-L1 blockers are an established treatment for many solid cancers. There are currently no approved ICIs for sarcomas, but satisfactory results have been seen in some patients with disseminated disease in certain histological types. Most studies on PD-L1 in sarcoma have used small specimens and there...
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... characteristics and visualization of PD-L1 staining is demonstrated in Figure 1. The majority of CS were PD-L1-negative (Table 1). ...
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... immunoreactivity was more common in tumors with higher histological grade (grade 3 or dedifferentiated) and not observed in any grade 2 tumors. Three tumors also showed >50% immunoreactivity in TC using SP263 ( Figure A1). The presence of immune cells (IC) was rare; 22 cases had IC present, and only two cases had ≥1% immunoreactivity (Table 1, Figure A1). ...
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... tumors also showed >50% immunoreactivity in TC using SP263 ( Figure A1). The presence of immune cells (IC) was rare; 22 cases had IC present, and only two cases had ≥1% immunoreactivity (Table 1, Figure A1). Univariate analysis showed that higher age and tumor grade were significantly associated with shorter MFS and OS (Figures 2 and A2). ...
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... was no significant correlation between PD-L1 immunoreactivity and clinical outcome; Kaplan-Meier analysis showed that patients with PD-L1-positive tumors had shorter OS, but the difference was nonsignificant and most likely explained by the association to high tumor grade (Figure 3). Figure 1. (A) Magnetic resonance imaging depicting chondrosarcoma (CS) in the humerus (arrow) and (B) histology of high-grade CS stained with (C) SP142 and (D) SP263 assays at ×200 magnification showing a higher number of cells with PD-L1 immunoreactivity using the SP263 assay. ...
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... characteristics and visualization of PD-L1 staining is demonstrated in Figure 4. Most tumors had either none or low immunoreactivity with SP142 and none, low or intermediate with SP263 (Table 1). One tumor had >50% PD-L1 immunoreactivity in TC using SP263 ( Figure A1). Immune infiltrate was present in 48 cases; 35 cases expressed ≥1% immunoreactivity with SP263 and 34 cases with SP142 (Table 1, Figure A1). ...
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... tumor had >50% PD-L1 immunoreactivity in TC using SP263 ( Figure A1). Immune infiltrate was present in 48 cases; 35 cases expressed ≥1% immunoreactivity with SP263 and 34 cases with SP142 (Table 1, Figure A1). (Table 1, Figure A1). ...
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... infiltrate was present in 48 cases; 35 cases expressed ≥1% immunoreactivity with SP263 and 34 cases with SP142 (Table 1, Figure A1). (Table 1, Figure A1). ...
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... characteristics and visualization of PD-L1 staining are demonstrated in Figure 5. PD-L1 immunoreactivity was more common in UPS (Table 1) compared to CS and LS (p < 0.05). Furthermore, >50% immunoreactivity was seen in two and eight tumors using the SP142 and SP263 assay, respectively ( Figure A1). Immune cells were observed in 68 cases with 43 and 52 cases expressing ≥1% immunoreactivity with SP142 and SP263, respectively (Table 1, Figure A1). ...
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... >50% immunoreactivity was seen in two and eight tumors using the SP142 and SP263 assay, respectively ( Figure A1). Immune cells were observed in 68 cases with 43 and 52 cases expressing ≥1% immunoreactivity with SP142 and SP263, respectively (Table 1, Figure A1). Biomolecules 2022, 12, x 8 of 17 ...
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... characteristics and visualization of PD-L1 staining are demonstrated in Figure 5. PD-L1 immunoreactivity was more common in UPS (Table 1) compared to CS and LS (p < 0.05). Furthermore, >50% immunoreactivity was seen in two and eight tumors using the SP142 and SP263 assay, respectively ( Figure A1). Immune cells were observed in 68 cases with 43 and 52 cases expressing ≥1% immunoreactivity with SP142 and SP263, respectively (Table 1, Figure A1). ...
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Citations
... 28 PD-L1 expression in CS has also been positively correlated with expression of Ki-67 and TP53 in CS. 29 In another study, tissue analysis demonstrated PD-1 expression in 9/10 samples from CS tumors but a lack of PD-L1 expression. 30 Further, Zhang et al. 31 demonstrated that while the majority of tumor cells from CS samples are PD-L1 negative, positive expression was associated with higher histologic grade, either grade 3 or dedifferentiated. While lack of tissue PD-L1 expression detectable by IHC does not preclude conventional CS responses to anti-PD-L1 agents, these studies do suggest anti-PD-1 agents such as pembrolizumab may be effective in most low-grade subtypes of CS. 32,33 Immune infiltrate. ...
Chondrosarcomas (CSs) consist of a heterogenous group of primary bone cancers arising from malignant cells which produce cartilaginous matrix. As the second most common primary bone cancer, CS are often resistant to systemic chemotherapy due to poor vascularization, slow proliferation, and expression of multidrug-resistant pumps. Immune checkpoint inhibitors have transformed the field of oncology and are now designated as frontline therapy for many solid tumor cancers. Several studies have demonstrated increased expression of programed cell death 1 (PD-1) and PD-L1 in CS tissue in vitro, which has led to the development of multiple clinical trials for immunotherapy in patients with aggressive CS. In this review, we highlight the ongoing investigation into the role for immunotherapy in CS. We also report the case of a 44-year-old female with a history of stage IV primary CS of the right shoulder who underwent radical resection with recurrence and demonstrated a spectacular sustained response to pembrolizumab at our center. Our review highlights the need for further studies investigating the role of immunotherapy in the treatment of aggressive bone sarcomas that are resistant to standard surgical resection, chemotherapy, and radiation treatment.
... PD-1/PD-L1 interaction is the main pathway of immune control of tumor suppression, and PD-1 has gradually become a hot topic for research (48). PD-1/PD-L1-related immune responses are more common in UPS (49,50), but more as a differential diagnosis, one of the methods that has limitations for the prognosis prediction of the disease (51). In a study by YangYou et al., anti-angiogenesis inhibitors combined with PD-1 inhibitors had a good effect on UPS (52), and in a study by Zhichao Tian et al., paclitaxel combined with PD-1 inhibitors also had a significant effect on UPS (53), but some patients had poor results with PD-1 inhibitors (54). ...
Background
Undifferentiated pleomorphic sarcoma (UPS) is a highly malignant soft tissue sarcoma with a poor prognosis and no clear effective clinical means for treatment, and there has been no significant progress in research within this field in recent years. This study aimed to investigate the epidemiology, etiology, clinical features, diagnostic modalities, various treatment modalities, and prognosis of retroperitoneal undifferentiated pleomorphic sarcoma and to contribute to the clinical management of this type of disease. In this study, we report a case of undifferentiated pleomorphic sarcoma with a primary origin in the retroperitoneum. Undifferentiated pleomorphic sarcoma occurring in the retroperitoneum is rarely reported.
Case description
A 59-year-old man with abdominal distension and pain for 4 months presented to our hospital after the failure of conservative treatment. A 9.6 cm by 7.4 cm mass in the left retroperitoneum was found on a CT scan of the whole abdomen with three degrees of enhancement. After surgical treatment, the tumor and the left kidney were completely removed, and pathological examination and genetic sequencing showed an apparent undifferentiated pleomorphic sarcoma. The patient subsequently declined follow-up treatment and is currently alive and well.
Conclusions
At the current level of clinical technology, the treatment of undifferentiated pleomorphic sarcoma is still in the exploratory stage, and the scarcity of clinical cases of this disease may have hindered the acquisition of clinical trials and research data for this disease. At present, the first choice of treatment for undifferentiated pleomorphic sarcoma is still radical resection. In the existing clinical studies, there are no strong data to support the effect of preoperative neoadjuvant chemoradiotherapy and adjuvant chemoradiotherapy in clinical practice. Similar to other diseases, the use of radiotherapy and chemotherapy before and after surgery may be a potential treatment for this disease in the future. Targeted therapy for this disease still needs further exploration, and we need more reports on related diseases to promote future treatment and research on this disease.
... In recent years, targeted therapies using immune checkpoint inhibitors (ICIs) to block the binding between programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) achieved good responses in various malignancies such as lung cancer (6) and melanoma (7). Monoclonal antibodies against PD-1 and PD-L1 can activate T lymphocytes by blocking the PD-1/PD-L1 signaling pathway, thereby preventing tumors from achieving immune evasion (8). Treatment response is often associated with the presence of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor and immune cells (9). ...
... STS is generally described as having low PD-L1 expression with response rates range 5%-18% (11,38). Sarcomas with PD-L1 expression include angiosarcoma, chondrosarcoma, Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and UPS, among which high PD-L1 expression tends to be more common in UPS (8,34). Zhang et al. (8), used the SP263 assay to measure PD-L1 expression in chondrosarcoma, liposarcoma, and UPS, respectively, and observed increased response rates in the UPS group, with TPS >50% observed in 8 tumors (8/96). ...
... Sarcomas with PD-L1 expression include angiosarcoma, chondrosarcoma, Ewing's sarcoma, rhabdomyosarcoma, synovial sarcoma, and UPS, among which high PD-L1 expression tends to be more common in UPS (8,34). Zhang et al. (8), used the SP263 assay to measure PD-L1 expression in chondrosarcoma, liposarcoma, and UPS, respectively, and observed increased response rates in the UPS group, with TPS >50% observed in 8 tumors (8/96). To our knowledge, there are very few reports of PD-1 inhibitors for UPS PD-L1 high expression. ...
Undifferentiated pleomorphic sarcoma (UPS) is a rare and aggressive soft tissue tumor with a high degree of malignancy and rapid progression, usually occurring in the extremities, retroperitoneum, and abdomen, whereas it rarely arises in the mediastinum, and is treated mainly by surgical resection. The prognosis of patients with advanced sarcoma is poor, and doxorubicin monotherapy is the standard first-line chemotherapy for most advanced soft tissue sarcomas (STS), but the prognosis is generally unsatisfactory. Immune checkpoint inhibitors (ICIs) have been established as therapies for many solid cancers in recent years; however, evidence on the efficacy of ICIs in undifferentiated sarcoma is scarce, mostly consisting of small studies, and no ICIs are currently approved for use in sarcomas. We report a case of a middle-aged man with primary mediastinal UPS with high PD-L1 expression (TPS was approximately 80%) and TLS positive. The patient was treated with sequential tislelizumab monotherapy maintenance after 6 cycles of tislelizumab combined with epirubicin, efficacy evaluation was partial remission (PR), progression-free survival (PFS) was 8.5 months, and grade 1 fatigue was identified as an adverse event.
... The presence of tumor-infiltrating lymphocytes and PD-L1 expression are both generally promoted by anti PD-1/L1 blockade [10]. However, Zhang et al. found no significant difference in metastasis-free or overall survival in cases of liposarcoma, regardless of PD-L1 expression [11]. The effectiveness of immune checkpoint blockade therapy has recently been investigated in an open-label phase II study of anti-PD-1 monotherapy in patients with histological evidence of metastatic or surgically unresectable locally advanced sarcoma. ...
An 80-year-old man presented to our emergency department complaining of a mass on the right side of his chest and pain in the right flank of his back. A chest computed tomography (CT) scan showed a relatively heterogenous oval-shaped tumor measuring 7.5 × 6.0 cm eroded to the 8th rib, with slightly dense fluid accumulation inside and calcification of the tumor wall. A 1-month follow-up CT scan showed spontaneous shrinkage of the tumor. The tumor was completely excised from the thoracic wall and the wall was reconstructed with a polytetrafluoroethylene mesh. Pathological examination showed coagulation necrosis in the chest wall tumor, but immunohistochemical staining revealed murine double minute 2- and Cyclin-dependent kinase 4-positive cells with irregular nuclear size and bizarre morphology. Therefore, dedifferentiated liposarcoma (DDLPS) was the final pathological diagnosis. Remarkable infiltration of CD8+ lymphocytes into the tumor was observed, along with a 90% positive ratio for programmed cell death-ligand 1. The patient has been followed-up for 1 year without any recurrence, despite not receiving any additional treatment. Liposarcoma is one of the most common types of soft tissue sarcomas; however, spontaneous regression of primary DDLPS arising from the chest wall is extremely rare. Herein, we report a case of DDLPS primary to the chest wall with spontaneous regression, probably due to a spontaneously induced T cell response.
Epithelial-mesenchymal transformation (EMT) plays a pivotal role in embryonic development, tissue fibrosis, repair, and tumor invasiveness. Emerging studies have highlighted the close association between EMT and immune checkpoint molecules, particularly programmed cell death ligand 1 (PDL1). PDL1 exerts its influence on EMT through bidirectional regulation. EMT-associated factors, such as YB1, enhance PDL1 expression by directly binding to its promoter. Conversely, PDL1 signaling triggers downstream pathways like PI3K/AKT and MAPK, promoting EMT and facilitating cancer cell migration and invasion. Targeting PDL1 holds promise as a therapeutic strategy for EMT-related diseases, including cancer and fibrosis. Indeed, PDL1 inhibitors, such as pembrolizumab and nivolumab, have shown promising results in clinical trials for various cancers. Recent research has also indicated their potential benefit in fibrosis treatment in reducing fibroblast activation and extracellular matrix deposition, thereby addressing fibrosis. In this review, we examine the multifaceted role of PDL1 in immunomodulation, growth, and fibrosis promotion. We discuss the challenges, mechanisms, and clinical observations related to PDL1, including the limitations of the PD1/PDL1 axis in treatment and PD1-independent intrinsic PDL1 signaling. Our study highlights the dynamic changes in PDL1 expression during the EMT process across various tumor types. Through interplay between PDL1 and EMT, we uncover co-directional alterations, regulatory pathways, and diverse changes resulting from PDL1 intervention in oncology. Additionally, our findings emphasize the dual role of PDL1 in promoting fibrosis and modulating immune responses across multiple diseases, with potential implications for therapeutic approaches. We particularly investigate the therapeutic potential of targeting PDL1 in type II EMT fibrosis: strike balance between fibrosis modulation and immune response regulation. This analysis provides valuable insights into the multifaceted functions of PDL1 and contributes to our understanding of its complex mechanisms and therapeutic implications.
