The emerging role of immunotherapy for the treatment of sarcoma

Klemen, Nicholas D.; Kelly, Ciara M.; Bartlett, Edmund K.

doi:10.1002/jso.26306

Cited by 17 publications

(17 citation statements)

References 88 publications

(163 reference statements)

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“…At present, the clinical indications of immunotherapy are more and more extensive, and it has become the leading treatment for metastatic diseases ( 41 ). Despite that the field cancer immunotherapy was founded by clinicians caring for sarcoma patients, the response of immunotherapy for sarcoma varies because of its various histological origin and immune microenvironment ( 40 , 42 ). A phase II trial of pembrolizumab in patients with selected STSs and bone sarcomas was carried out by Tawbi et al ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

The Role of Radiotherapy in Soft Tissue Sarcoma on Extremities With Lymph Nodes Metastasis: An IPTW Propensity Score Analysis of the SEER Database

Qiu

Zeng

et al. 2021

Front. Oncol.

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BackgroundSoft tissue sarcomas on extremities with regional lymph nodes metastasis (STSE-RLNM) is a devastating situation. Optimizing therapeutic approaches is vital but hampered by a shortage of randomized trials. We used a population-level database to evaluate radiotherapy’s impact on sarcoma-specific survival (SSS) and overall survival (OS) for surgery for STSE-RLNM.MethodsWe retrospectively screened data from the SEER database (2004–2015), and 265 patients with STSE-RLNM who received surgery, with (134) or without (131) radiotherapy, were enrolled in this study. A propensity-score-matched analysis with the inverse probability of treatment weighting (IPTW) Kaplan–Meier curve was created. The log-rank test and Cox regression analysis were performed to compare SSS and OS in patients with and without radiotherapy. Further analysis of radiotherapy time was conducted, and the Kaplan–Meier curve and the log-rank test were done. Landmark analysis was introduced to attenuate the immortal bias.ResultsIn the original unadjusted cohort, the radiotherapy + surgery group is associated with improved SSS [hazard ratio (HR), 0.66; 95% CI, 0.47–0.91; p = 0.011] and OS (HR, 0.64; 95% CI, 0.47–0.88; p = 0.006). This significant treatment effect was also noted in IPTW-adjusted Cox regression either on SSS (HR, 0.65; 95% CI, 0.45–0.93; p = 0.020) or on OS (HR, 0.64; 95% CI, 0.46–0.91; p = 0.013). The Kaplan–Meier curve and log-rank test showed that pre- and postoperative radiotherapy was not related to SSS (p = 0.980 or OS (p = 0.890).ConclusionRadiotherapy and surgery has a significant benefit on the prognosis of patients with STSE-RLNM compared to surgery alone. These findings should be considered when making treatment decisions for them.

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Section: Discussionmentioning

confidence: 99%

The Role of Radiotherapy in Soft Tissue Sarcoma on Extremities With Lymph Nodes Metastasis: An IPTW Propensity Score Analysis of the SEER Database

Qiu

Zeng

et al. 2021

Front. Oncol.

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“…Surgical resection and radiotherapy are cornerstone treatments in this area since these are chemo-resistant tumors [5]. However, immunotherapy could be a possible option for chordoma patients, as for patients with other types of sarcomas [6], with some promising results being shown in the rare cases reported [7]. Currently, a phase I trial of nivolumab with or without stereotactic radiosurgery in chordoma patients is taking place (ClinicalTrials.gov Identifier: NCT02989636).…”

Section: Introductionmentioning

confidence: 99%

The Immune Microenvironment of Chordomas: An Immunohistochemical Analysis

Dridi

Krebs-Drouot

Meyronet

et al. 2021

Cancers

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Chordomas are rare sarcomas that are usually treated by surgery and/or radiotherapy since these are chemo-resistant tumors, but immunotherapy could be a possible option for chordoma patients. However, few reports investigating the composition of the chordoma immune microenvironment exist. We immunohistochemically studied 81 chordomas regarding their immune microenvironment factors and compared them with clinicopathological data. Macrophages and CD4 cells were the most prominent inflammatory cell populations, followed by CD8 T cells, while CD20 B cells and high endothelial venules (MECA-79+) were less frequently found. PD-L1 (22C3) expression by inflammatory cells was found in 21 (26%) tumors and was associated with a larger tumor size. None of the cases showed the expression of PD-L1 by tumor cells. Survival analysis showed that younger patients had a better overall survival. Considering the immunohistochemical factors studied, higher CD8, the presence of PD-L1+ immune cells, and higher vascular density were adverse prognostic factors, but in multivariate analysis, only PD-L1+ immune cells retained prognostic significance. To conclude, chordoma tumor cells do not express PD-L1, but PD-L1+ immune cells seem to play a negative prognostic role, supporting the need for further studies in this field and the possible beneficial role of immunotherapy in these patients.

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“…Immunotherapy for sarcoma (Coley's toxins, IL‐2, adoptive T‐cell transfer, and immune checkpoint blockade) showed limited success. Ongoing research is studying the combined use of immune checkpoint blockade with other immune modulators, surgery, or radiation 288 . In a rat experimental model bearing BN‐175 tumors the association of histamine and IL‐2 in the melphalan‐based isolated limb perfusion setting showed no improved response (40 µg melphalan, 1 mg histamine, and 50 µg IL‐2 in 5 ml total volume perfusate) 289 …”

Section: Histamine As An Adjuvant To Cancer Immunotherapymentioning

confidence: 99%

Histamine in cancer immunology and immunotherapy. Current status and new perspectives

Sarasola

Delgado

Nicoud

et al. 2021

Pharmacology Res & Perspec

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Cancer is the second leading cause of death globally and its incidence and mortality are rapidly increasing worldwide. The dynamic interaction of immune cells and tumor cells determines the clinical outcome of cancer. Immunotherapy comes to the forefront of cancer treatments, resulting in impressive and durable responses but only in a fraction of patients. Thus, understanding the characteristics and profiles of immune cells in the tumor microenvironment (TME) is a necessary step to move forward in the design of new immunomodulatory strategies that can boost the immune system to fight cancer. Histamine produces a complex and fine‐tuned regulation of the phenotype and functions of the different immune cells, participating in multiple regulatory responses of the innate and adaptive immunity. Considering the important actions of histamine‐producing immune cells in the TME, in this review we first address the most important immunomodulatory roles of histamine and histamine receptors in the context of cancer development and progression. In addition, this review highlights the current progress and foundational developments in the field of cancer immunotherapy in combination with histamine and pharmacological compounds targeting histamine receptors.

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The emerging role of immunotherapy for the treatment of sarcoma

Cited by 17 publications

References 88 publications

The Role of Radiotherapy in Soft Tissue Sarcoma on Extremities With Lymph Nodes Metastasis: An IPTW Propensity Score Analysis of the SEER Database

The Role of Radiotherapy in Soft Tissue Sarcoma on Extremities With Lymph Nodes Metastasis: An IPTW Propensity Score Analysis of the SEER Database

The Immune Microenvironment of Chordomas: An Immunohistochemical Analysis

Histamine in cancer immunology and immunotherapy. Current status and new perspectives

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