Is immunotherapy in the future of therapeutic management of sarcomas?

Clemente, Ottavia; Ottaiano, Alessandro; Lorenzo, Giuseppe Di; Bracigliano, Alessandra; Lamia, Sabrina; Cannella, Lucia; Pizzolorusso, Antonio; Marzo, Massimiliano Di; Santorsola, Mariachiara; Chiara, Annarosaria De; Fazioli, Flavio; Tafuto, Salvatore

doi:10.1186/s12967-021-02829-y

Cited by 21 publications

(17 citation statements)

References 154 publications

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“…Although recent evidence shows that the response rate of PD-1 inhibitor monotherapy is low in patients with STS [17,18], there have been encouraging reports of efficacy in some sarcoma subtypes [19]. The combination of PD-1 inhibitors with cytotoxic chemotherapy agents is a promising way to improve the efficacy of PD-1 inhibitors in the treatment of patients with malignant tumors, including STS [18,[20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study

et al. 2022

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Background There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited. Methods The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan–Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant. Results A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8–3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018). Conclusion Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.

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Section: Introductionmentioning

confidence: 99%

Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study

et al. 2022

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“…The prevailing view is that hot tumors are the ones most likely to benefit from ICI therapy [ 60 ]. Since IS2 and IS4 have pre-existing immune infiltration and highly expressed ICP-related genes, the use of ICI to improve immunosuppressed TIMEs and thus enhance the pre-existing antitumor immunity might be beneficial in a combinatory approach, as only a small proportion of STS patients benefited from ICI monotherapy [ 14 , 61 , 62 ]. In clinical trial SARC028, 40% of UPS and only 20% of DDLPS patients responded to ICI therapy [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Tumor Antigens and Immune Subtypes for the Development of mRNA Vaccines and Individualized Immunotherapy in Soft Tissue Sarcoma

Duan

Gong

et al. 2022

Cancers

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Soft tissue sarcomas (STS) are a rare disease with high recurrence rates and poor prognosis. Missing therapy options together with the high heterogeneity of this tumor type gives impetus to the development of individualized treatment approaches. This study identifies potential tumor antigens for the development of mRNA tumor vaccines for STS and explores potential immune subtypes, stratifying patients for immunotherapy. RNA-sequencing data and clinical information were extracted from 189 STS samples from The Cancer Genome Atlas (TCGA) and microarray data were extracted from 103 STS samples from the Gene Expression Omnibus (GEO). Potential tumor antigens were identified using cBioportal, the Oncomine database, and prognostic analyses. Consensus clustering was used to define immune subtypes and immune gene modules, and graph learning-based dimensionality reduction analysis was used to depict the immune landscape. Finally, four potential tumor antigens were identified, each related to prognosis and antigen-presenting cell infiltration in STS: HLTF, ITGA10, PLCG1, and TTC3. Six immune subtypes and six gene modules were defined and validated in an independent cohort. The different immune subtypes have different molecular, cellular, and clinical characteristics. The immune landscape of STS reveals the immunity-related distribution of patients and intra-cluster heterogeneity of immune subtypes. This study provides a theoretical framework for STS mRNA vaccine development and the selection of patients for vaccination, and provides a reference for promoting individualized immunotherapy.

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“…CAR-T immunotherapy offers an adoptive therapy that uses gene-transfer technology to engineer traditional T-lymphocytes into conventional T cells [ 8 ]. The primary goal is to adjust the patient's DNA by introducing the gene coding for chimeric antigen receptor (CAR), rendering them specifically to eliminate cancer cells without needing an MHC [ 20 ]. This feature serves essential since a major component causing tumor progression in OS is the decrease in MHC class I expression [ 17 ].…”

Section: Reviewmentioning

confidence: 99%

“…This domain provides stability to the receptor via the hinge derived from CD8 or immunoglobulin (Ig4) molecules, their most crucial component. Finally, the endodomain is responsible for activating the T cells once CAR binds to the target antigen, thereby allowing for the intracellular T-cell receptor (TCR) signaling [ 8 , 20 ].…”

Section: Reviewmentioning

confidence: 99%

A Deep Dive Into the Newest Avenues of Immunotherapy for Pediatric Osteosarcoma: A Systematic Review

Suri¹,

Soni²,

Okpaleke³

et al. 2021

Cureus

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Osteosarcoma (OS) is the most common primary bone cancer affecting children and young adults, most often occurring at the metaphysis of long bones. At present, treatment with combinations of surgery and chemotherapy for the localized OS has only brought minuscule improvements in prognosis. In comparison, the advanced, metastatic, or recurrent forms of OS are often non-responsive to chemotherapy, adding to the dire need to develop new and efficient therapies.The question of interest investigated in this systematic review is whether immunotherapy can play a meaningful role in improving the clinical outcomes of children with OS. This article aims to summarize the preclinical and clinical research conducted thus far on potential therapeutic avenues for pediatric OS using immunotherapy, including methods like checkpoint inhibition, adoptive cellular therapy with T-cells, chimeric antigen receptor T (CAR-T), and natural killer (NK) cells. It also highlights the influence of the innate and adaptive immune system on the tumor microenvironment, allowing for OS progression and metastasis.This systematic review contains 27 articles and analyses of multiple clinical trials employing immunotherapeutic drugs to 785 osteosarcoma participants and over 243 pediatric patients. The articles were obtained through PubMed, PubMed Central, and ClinicalTrials.gov and individually assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist and the Cochrane risk-of-bias tool. The reviews reveal that immunotherapy's most significant impact on pediatric OS includes combining immune checkpoint blockers with traditional chemotherapy and surgery. However, due to the bimodal distribution of this aggressive malignancy, these studies cannot precisely estimate the overall effect and any potential life-threatening adverse events following therapy in children. Further research is required to fully assess the impact of these immunotherapies, including more extensive multinational clinical trials to focus on the pediatric population.

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Is immunotherapy in the future of therapeutic management of sarcomas?

Cited by 21 publications

References 154 publications

Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study

Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study

Identification of Tumor Antigens and Immune Subtypes for the Development of mRNA Vaccines and Individualized Immunotherapy in Soft Tissue Sarcoma

A Deep Dive Into the Newest Avenues of Immunotherapy for Pediatric Osteosarcoma: A Systematic Review

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