Intratumoral Therapy to Make a ?Cold? Tumor ?Hot?: The Jury Is Still Out

Review Oncology

Central Role of the Antigen-Presentation and Interferon-γ Pathways in Resistance to Immune Checkpoint Blockade

Annette Paschen et al.

Summary: Resistance to immunotherapy is often caused by acquired stealth mechanisms of tumor cells, such as loss of MHC class I expression or downregulation of antigen presentation pathways. Mutations in molecules involved in interferon-gamma signaling lead to unresponsiveness to IFN gamma and loss of recognition and killing by cytotoxic T lymphocytes. However, this mechanism also increases the sensitivity of tumor cells to natural killer cells, which could be exploited to overcome resistance.

ANNUAL REVIEW OF CANCER BIOLOGY (2022)

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Article Oncology

Tilsotolimod Exploits the TLR9 Pathway to Promote Antigen Presentation and Type 1 IFN Signaling in Solid Tumors: A Multicenter International Phase I/II Trial (ILLUMINATE-101)

Hani Babiker et al.

Summary: This study investigated the safety, dose, efficacy, and immune effects of the investigational synthetic Toll-like receptor 9 (TLR9) agonist Tilsotolimod in multiple solid tumors. The results showed that Tilsotolimod monotherapy was generally well tolerated and induced rapid, significant alterations in the tumor microenvironment.

CLINICAL CANCER RESEARCH (2022)

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Meeting Abstract Oncology

FINAL ANALYSIS: PHASE 1B STUDY INVESTIGATING INTRATUMORAL INJECTION OF TOLL-LIKE RECEPTOR 9 AGONIST VIDUTOLIMOD ± PEMBROLIZUMAB IN PATIENTS WITH PD-1 BLOCKADE-REFRACTORY MELANOMA

John Kirkwood et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Meeting Abstract Oncology

MASTERKEY-265: A phase III, randomized, placebo (Pbo)-controlled study of talimogene laherparepvec (T) plus pembrolizumab (P) for unresectable stage IIIB-IVM1c melanoma (MEL)

A. Ribas et al.

ANNALS OF ONCOLOGY (2021)

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Article Oncology

Overcoming PD-1 Blockade Resistance with CpG-A Toll-Like Receptor 9 Agonist Vidutolimod in Patients with Metastatic Melanoma

Antoni Ribas et al.

Summary: In patients with advanced melanoma, combining intratumoral TLR9 agonist vidutolimod with pembrolizumab showed promising clinical activity and manageable safety profile, indicating potential to overcome resistance to PD-1 blockade through IFN response induction.

CANCER DISCOVERY (2021)

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Review Immunology

Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity

Filippo Veglia et al.

Summary: MDSCs are pathologically activated cells with potent immunosuppressive activity, closely associated with poor clinical outcomes in diseases like cancer. Recent studies have identified key distinctions between MDSCs and classical neutrophils and monocytes, providing new insights into therapeutic targeting for cancer and autoimmune diseases through understanding their genomic and metabolic characteristics. Emerging data also suggest potential involvement of MDSCs in pregnancy, neonatal biology, and COVID-19.

NATURE REVIEWS IMMUNOLOGY (2021)

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Meeting Abstract Oncology