Immunotherapy in soft tissue and bone sarcoma: unraveling the barriers to effectiveness

Abstract

Sarcomas are uncommon malignancies of mesenchymal origin that can arise throughout the human lifespan, at any part of the body. Surgery remains the optimal treatment modality whilst response to conventional treatments, such as chemotherapy and radiation, is minimal. Immunotherapy has emerged as a novel approach to treat different cancer types but efficacy in soft tissue sarcoma and bone sarcoma is limited to distinct subtypes. Growing evidence shows that cancer-stroma cell interactions and their microenvironment play a key role in the effectiveness of immunotherapy. However, the pathophysiological and immunological properties of the sarcoma tumor microenvironment in relation to immunotherapy advances, has not been broadly reviewed. Here, we provide an up-to-date overview of the different immunotherapy modalities as potential treatments for sarcoma, identify barriers posed by the sarcoma microenvironment to immunotherapy, highlight their relevance for impeding effectiveness, and suggest mechanisms to overcome these barriers.

A comparative study between two methods of delivery of chemotherapeutic agent in patients with bone and soft tissue sarcoma of lower extremity

“…Currently, immunotherapy is a contentious problem in the treatment of bone and soft tissue tumors, which relies on stimulating the host immune system’s natural defense to attack and kill malignant cells. Immunotherapy’s mechanism differs from that of chemotherapy [ 6 ]. Compared with traditional treatment methods, such as surgery, radiotherapy, and chemotherapy, immunotherapy is more effective in curing the root cause and exhibits high selectivity, selectively killing malignant cells and reducing the damage to normal tissues [ 7 , 8 ].…”

Tumor microenvironment phenotypes and prognostic evaluation tools for osteosarcoma characterized by different prognostic outcomes and immunotherapy responses

“…Models of immunotherapy include adoptive cell therapy, immune checkpoint inhibitors, in situ vaccination such as oncolytic virotherapy, and cancer vaccines. 5 Although more and more patients with osteosarcoma benefit from immunotherapy, the heterogeneity and complexity of this pathology greatly hinder the effectiveness of immunotherapy. 4 Therefore, it is necessary to deeply study and explore the immunological characteristics and pathological environment involved in immunotherapy to improve the effectiveness of immunotherapy.…”

“…Its pathophysiological and immunological characteristics are related to the progress of immunotherapy. 5,6 Multiple studies have provided novel and valuable insights into tumor heterogeneity and the multifaceted mechanisms of immunotherapy by characterizing TME. 7 By summarizing the study of immunotherapy and TME immunity and tumor biology, Chen 9 and Bagaev et al 10 has done so.…”

“…Immunotherapy relies on stimulating the natural defenses of the natural defenses of the host immune system to attack malignant cells, which functions differently from chemotherapy that directly kills cancer cells. Models of immunotherapy include adoptive cell therapy, immune checkpoint inhibitors, in situ vaccination such as oncolytic virotherapy, and cancer vaccines 5 . Although more and more patients with osteosarcoma benefit from immunotherapy, the heterogeneity and complexity of this pathology greatly hinder the effectiveness of immunotherapy 4 .…”

“…The tumor microenvironment (TME) is a “complex network” including different cell types, soluble factors, signal molecules and extracellular matrix components. Its pathophysiological and immunological characteristics are related to the progress of immunotherapy 5,6 . Multiple studies have provided novel and valuable insights into tumor heterogeneity and the multifaceted mechanisms of immunotherapy by characterizing TME 7 .…”