Cancer immunotherapy with immune checkpoint inhibitors (ICIs) targeting PD-1 or CTLA-4 has demonstrated a potent and durable therapeutic efficacy and emerged as a new weapon in the war on cancer. However, the clinical efficacy of ICIs is confined to tumors with a T cell–inflamed tumor microenvironment (TME). In poorly immunogenic tumors with few tumor-infiltrating lymphocytes (TILs), TME lacks the type I interferon signature and chemokines for T cell recruitment. Moreover, tumor vasculatures and stromal components may pose a barrier against intratumoral trafficking of T cells and their effector functions on tumor cells.

Therefore, additional therapeutic interventions are required for these non–T cell-inflamed tumors to appropriately remodel the TME to render these tumors more sensitive to ICI treatments.

Our team tries to develop novel therapeutic strategies that can lead to an immunological “boiling point” in which a cold, non-inflamed tumor is sufficiently inflamed to enable the host immune system to eradicate tumor cells through various immunotherapeutic combinations.

1. Promote innate immunity/type I IFN signaling

• • Intratumoral STING agonists

  • Oncolytic viruses

  • TLR agonists

2. Modulate tumor microenvironment and enhances T cell trafficking

• • Vascular targeting agents against VEGF/VEGFR2 signaling

  • Ectopic lymphoid organs and High endothelial venules

3. Eliminate immune suppression

• • IDO/TDO selective inhibitors