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Review
. 2018 Oct 1;124(19):3819-3829.
doi: 10.1002/cncr.31517. Epub 2018 May 3.

Rationale and emerging strategies for immune checkpoint blockade in soft tissue sarcoma

Amy J Wisdom  1 , Yvonne M Mowery  2 , Richard F Riedel  3 , David G Kirsch  1   2
Affiliations
Review

Rationale and emerging strategies for immune checkpoint blockade in soft tissue sarcoma

Amy J Wisdom et al. Cancer. .

Abstract

Soft tissue sarcomas (STS) are heterogeneous, mesenchymal malignancies with variable biologic behavior. The primary management for localized STS is surgical resection, which may be combined with neoadjuvant or adjuvant radiation therapy to increase the probability of achieving local control. Many patients with large, high-grade STS develop metastatic disease. Several clinical trials of immune checkpoint blockade for STS have produced promising responses in patients with metastatic disease. In this review, recent and ongoing clinical trials of immune checkpoint inhibition for STS are discussed. The authors explain the rationale for immune checkpoint inhibition and radiation therapy and highlight new studies testing this combination in the neoadjuvant setting for patients with high-risk STS. In addition, they describe novel combinations of immunotherapy with targeted therapies and chemotherapies being tested in the metastatic setting and discuss how these combinations have the potential to be integrated into adjuvant therapy in the future.

Keywords: anti-programmed cell death protein-1 (anti-PD-1); anticytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4); immune checkpoint blockade; immunotherapy; radiation therapy; soft tissue sarcoma.

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Figures

Figure 1
Figure 1. Abscopal response may eliminate micrometastatic disease in soft tissue sarcoma patients
In an abscopal response, the primary tumor (green) is treated with radiation therapy, which has been shown to generate a systemic immune response. The anti-tumor immune response is mediated by both CD4 and CD8 T cells (yellow). This response may be further enhanced by blocking the inhibitory checkpoints CTLA-4 (orange) and/or PD-1 (purple) on the surface of CD4 and CD8 T cells. By increasing activation and effector function of T cells, immune checkpoint blockade has the potential to eradicate both irradiated and non-irradiated tumor cells. This has the potential to dramatically improve outcomes for patients with soft tissue sarcoma by eradicating micrometastatic disease.
Figure 2
Figure 2
Pollack SM, He Q, Yearley JH, Emerson R, Vignali M, Zhang Y, et al. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer. 2017; doi:10.1002/cncr.30726
See this image and copyright information in PMC

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