Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision

Abstract

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor microenvironment. With this rapid clinical and scientific progress, the field of cancer immunotherapy is currently at a critical inflection point, with potential for exponential growth over the next decade. Recognizing this, the Society for Immunotherapy of Cancer convened a diverse group of experts in cancer immunotherapy representing academia, the pharmaceutical and biotechnology industries, patient advocacy, and the regulatory community to identify current opportunities and challenges with the goal of prioritizing areas with the highest potential for clinical impact. The consensus group identified seven high-priority areas of current opportunity for the field: mechanisms of antitumor activity and toxicity; mechanisms of drug resistance; biomarkers and biospecimens; unique aspects of novel therapeutics; host and environmental interactions; premalignant immunity, immune interception, and immunoprevention; and clinical trial design, endpoints, and conduct. Additionally, potential roadblocks to progress were discussed, and several topics were identified as cross-cutting tools for optimization, each with potential to impact multiple scientific priority areas. These cross-cutting tools include preclinical models, data curation and sharing, biopsies and biospecimens, diversification of funding sources, definitions and standards, and patient engagement. Finally, three key guiding principles were identified that will both optimize and maximize progress in the field. These include engaging the patient community; cultivating diversity, equity, inclusion, and accessibility; and leveraging the power of artificial intelligence to accelerate progress. Here, we present the outcomes of these discussions as a strategic vision to galvanize the field for the next decade of exponential progress in cancer immunotherapy.

Keywords: Education; Hematologic Malignancies; Immune modulatory; Immune related adverse event - irAE; Solid tumor.

Figure 1

Areas of opportunity in cancer immunotherapy.

Figure 2

Promising and novel immunotherapeutic strategies. CAR, chimeric antigen receptor; CTLA-4, cytotoxic T lymphocyte antigen-4; ICOS, inducible costimulator; LAG3, lymphocyte-activation gene 3; LILRB, leukocyte immunoglobulin-like receptor family; mRNA, messenger RNA; NK cell, natural killer cell; OX40, tumor necrosis factor receptor superfamily member 4; PD-(L)1, PD-1/PD-L1 axis; SLAMF7, SLAM family member 7; TCR, T cell receptor; TIGIT, T cell immunoreceptor with Ig and ITIM domains; TIM3, T cell immunoglobulin and mucin domain-containing protein 3; TME, tumor microenvironment; 4-1BB, tumor necrosis factor receptor superfamily member 9.

Figure 3

Host and environmental interactions that influence tumor immunotherapy. AI, artificial intelligence; GEMM, genetically engineered mouse model; TME, tumor microenvironment.

Figure 4

Premalignant immunity, immunoprevention, and immune-interception.

Figure 5

Cross-cutting tools for optimizing impact in cancer immunotherapy.