Dataset Information

Tumor and Peripheral Immune Status in Soft Tissue Sarcoma: Implications for Immunotherapy.

ABSTRACT: Soft Tissue Sarcomas (STS) are a heterogeneous and rare group of tumors. Immune cells, soluble factors, and immune checkpoints are key elements of the complex tumor microenvironment. Monitoring these elements could be used to predict the outcome of the disease, the response to therapy, and lead to the development of new immunotherapeutic approaches. Tumor-infiltrating B cells, Natural Killer (NK) cells, tumor-associated neutrophils (TANs), and dendritic cells (DCs) were associated with a better outcome. On the contrary, tumor-associated macrophages (TAMs) were correlated with a poor outcome. The evaluation of peripheral blood immunological status in STS could also be important and is still underexplored. The increased lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR), higher levels of monocytic myeloid-derived suppressor cells (M-MDSCs), and Tim-3 positive CD8 T cells appear to be negative prognostic markers. Meanwhile, NKG2D-positive CD8 T cells were correlated with a better outcome. Some soluble factors, such as cytokines, chemokines, growth factors, and immune checkpoints were associated with the prognosis. Similarly, the expression of immune-related genes in STS was also reviewed. Despite these efforts, only very little is known, and much research is still needed to clarify the role of the immune system in STS.

SUBMITTER: Sousa LM

PROVIDER: S-EPMC8345459 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Tumor and Peripheral Immune Status in Soft Tissue Sarcoma: Implications for Immunotherapy.

Sousa Luana Madalena LM Almeida Jani Sofia JS Fortes-Andrade Tânia T Santos-Rosa Manuel M Freitas-Tavares Paulo P Casanova José Manuel JM Rodrigues-Santos Paulo P

Cancers 20210801 15

Soft Tissue Sarcomas (STS) are a heterogeneous and rare group of tumors. Immune cells, soluble factors, and immune checkpoints are key elements of the complex tumor microenvironment. Monitoring these elements could be used to predict the outcome of the disease, the response to therapy, and lead to the development of new immunotherapeutic approaches. Tumor-infiltrating B cells, Natural Killer (NK) cells, tumor-associated neutrophils (TANs), and dendritic cells (DCs) were associated with a better ...[more]

PMID: 34359785

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Project description:Studying the tumor microenvironment and surrounding lymph nodes is the main focus of current immunological research on soft tissue sarcomas (STS). However, due to the restricted opportunity to examine tumor samples, alternative approaches are required to evaluate immune responses in non-surgical patients. Therefore, the purpose of this study was to evaluate the peripheral immune profile of STS patients, characterize patients accordingly and explore the impact of peripheral immunotypes on patient survival. Blood samples were collected from 55 STS patients and age-matched healthy donors (HD) controls. Deep immunophenotyping and gene expression analysis of whole blood was analyzed using multiparametric flow cytometry and real-time RT-qPCR, respectively. Using xMAP technology, proteomic analysis was also carried out on plasma samples. Unsupervised clustering analysis was used to classify patients based on their immune profiles to further analyze the impact of peripheral immunotypes on patient survival. Significant differences were found between STS patients and HD controls. It was found a contraction of B cells and CD4 T cells compartment, along with decreased expression levels of ICOSLG and CD40LG; a major contribution of suppressor factors, as increased frequency of M-MDSC and memory Tregs, increased expression levels of ARG1, and increased plasma levels of IL-10, soluble VISTA and soluble TIMD-4; and a compromised cytotoxic potential associated with NK and CD8 T cells, namely decreased frequency of CD56dim NK cells, and decreased levels of PRF1, GZMB, and KLRK1. In addition, the patients were classified into three peripheral immunotype groups: "immune-high," "immune-intermediate," and "immune-low." Furthermore, it was found a correlation between these immunotypes and patient survival. Patients classified as "immune-high" exhibited higher levels of immune-related factors linked to cytotoxic/effector activity and longer survival times, whereas patients classified as "immune-low" displayed higher levels of immune factors associated with immunosuppression and shorter survival times. In conclusion, it can be suggested that STS patients have a compromised systemic immunity, and the correlation between immunotypes and survival emphasizes the importance of studying peripheral blood samples in STS. Assessing the peripheral immune response holds promise as a useful method for monitoring and forecasting outcomes in STS.

Project description:Immune-checkpoint inhibitors have shown promising antitumor effects against certain types of cancer. However, specific immune-checkpoint inhibitors for patients with sarcoma have yet to be identified, whereas the immunological status of peripheral blood in patients with bone sarcoma and soft-tissue sarcoma (STS) remains unknown. In addition, it is unclear whether the immunological status from the peripheral blood could be used as a prognostic indicator. Therefore, the present study aimed to clarify the immunological status of peripheral blood samples derived from patients with bone sarcoma and STS. Immune monitoring was performed using the peripheral blood samples of 61 patients with no metastasis of high-grade sarcoma. A total of 25 patients with metastatic sarcoma were used for comparison. A total of 41 immune cell subsets were analyzed using multicolor-flow cytometry. The patients that did not have metastasis demonstrated higher quantities of monocytic myeloid-derived suppressor cells (M-MDSCs) and T cell immunoglobulin and mucin domain-3 (Tim-3)+ CD8+ T cells, which were significantly associated with poor disease-free survival (DFS) time, while higher quantities of NKG2D+ CD8+ T cells were significantly associated with improved DFS time. Multivariate Cox regression analysis demonstrated that the number of Tim-3+ CD8+ T cells was associated with lower DFS time. A significant association was also found between the number of M-MDSCs and progression-free survival (PFS) time in patients with metastasis. The results suggested the occurrence of immune surveillance, which indicated that the host immune reaction against cancer existed in patients with bone sarcoma and STS. Notably, a high number of M-MDSCs was associated with both DFS and PFS time, suggesting a strong prognostic value. The data suggested that the immune status of peripheral blood was associated with the prognosis in patients with sarcoma, as previously reported in patients with other cancer types. In summary, the results may assist with the development of novel strategies for sarcoma treatment, based on the use of biomarkers or immunotherapy.

Dataset Information

Tumor and Peripheral Immune Status in Soft Tissue Sarcoma: Implications for Immunotherapy.

Publications

Tumor and Peripheral Immune Status in Soft Tissue Sarcoma: Implications for Immunotherapy.

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