Immunotherapy in soft tissue sarcoma: current evidence and future perspectives in a variegated family of different tumor

ABSTRACT

Introduction

In the last few years, steps forward in the knowledge of the biology of soft tissue sarcomas (STS) have led to the development of new therapeutic strategies, including immunotherapy.

Areas covered

This review outlines the recent findings on immunological features and provides a synopsis of the results of clinical trials with different immunotherapy approaches in STS, discussing criticisms, and how the efficacy of immunotherapy could be improved.

Expert opinion

The heterogeneity of STS has limited generalized approaches of immunotherapy in the disease. Clinical decisions should encompass a comprehensive characterization of the tumor microenvironment (TME), marked by intra-histotype diversity. Profiling of immune cells, checkpoint molecules, and antigen target/HLA expression is deemed to reshape the classical histotype classification for a selection of the most appropriate immune-based treatment. In a synergistic view, tumor-directed treatments, designed on the genetic and epigenetic histotype make-up, should be monitored for their immunomodulant effect and applied to ensure or amplify immunotherapy response. In light of the dynamic nature of the TME, this immunomonitoring should be conducted at baseline and during treatment, for improved therapeutic decisions and rational sequence of treatment combination, pursuing an immunological marker approach by histotype guidance.

KEYWORDS:

• Soft tissue sarcoma
• advanced disease
• histotypes
• immunotherapy
• immune checkpoint inhibitors
• adoptive cell therapy
• PD1/PDL1
• tumor microenvironment

Article highlights

• Most phase II studies or retrospective series investigating the activity of PD-1 or PD-L1 inhibitors in STS have included an extremely histologically heterogeneous patient population, making it hard to get inside on the activity of ICIs in each single sarcoma type.

• While the overall efficacy of PD-1 and PD-L1 inhibitors is limited when all STS are taken together, there are a few sarcoma types that have shown sensitivity to immunotherapy, such as ASPS, UPS, and angiosarcoma.

• Different immunotherapeutic strategies, as adoptive cell therapy, appear to be a promising approach particularly in SS and MLPS.

• The monitoring of predictors of response/resistance and the highlight of novel combination strategies with the aim to sensitize STS to immune-targeting is warranted.

• The combination of a histology- and an immunological- marker-driven approach should be pursued, to help a better patient selection and a better clinical study design.

Declaration of interest

GG Baldi has received honoraria from Eli Lilly, Eisai, PharmaMar, GSK, and MSD; travel grants from PharmaMar, Pfizer, and Eli Lilly; and personal fees from AboutEvents, EditaMed, and Eli Lilly. A Gronchi has served on the Advisory Boards for Novartis, Pfizer, Bayer, Lilly, PharmaMar, and SpringWorks and received a research Grant from PharmaMar. S Stacchiotti honoraria from Bayer, Deciphera, Eli Lilly, Daiichi, Maxivax, and Novartis, invited speaker fees from GSK and PharmaMar, expert testimony fee from Bavarian Nordic and Epizyme, institutional research funding from Amgen Dompe, Advenchen, Bayer, Blueprint Medicines, Deciphera, Eli Lilly, Epizyme, Daiichi, GSK, Karyopharm, Novartis, Pfizer, PharmaMar, SpringWorks, and Hutchinson MediPharma International Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have no funding to report.