Abstract

Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer treatment, providing unprecedented clinical benefits. However, primary or acquired therapy resistance can affect up to two-thirds of patients receiving ICIs, underscoring the urgency to elucidate the mechanisms of treatment resistance and to design more effective therapeutic strategies. Conventional cancer treatments, including cytotoxic chemotherapy, radiation therapy, and targeted therapy, have immunomodulatory effects in addition to direct cancer cell-killing activities. Their clinical utilities in combination with ICIs have been explored, aiming to achieve synergetic effects with improved and durable clinical response. Here, we will review the immunomodulatory effects of chemotherapy, targeted therapy, and radiation therapy, in the setting of ICI, and their clinical implications in reshaping modern cancer immunotherapy.

Highlights

  • Deeper understanding in the regulatory mechanisms of antitumor immunity, especially the identification of immune checkpoint pathways, has led to the success of modern immunotherapy

  • The past decade has witnessed a revolution in cancer therapy since the introduction of immune checkpoint inhibitors (ICIs), including anti-CTLA4 antibody and anti-PD-1/PD-L1 antibody

  • These antibodies have reshaped the landscape of treatments in various types of cancers, including melanoma, renal cell cancer, colorectal cancer (CRC), and non-small-cell lung cancer (NSCLC)

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Summary

Combining immune Checkpoint inhibitors with Conventional Cancer Therapy

Yiyi Yan1*, Anagha Bangalore Kumar 2, Heidi Finnes 3, Svetomir N. Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer treatment, providing unprecedented clinical benefits. Primary or acquired therapy resistance can affect up to two-thirds of patients receiving ICIs, underscoring the urgency to elucidate the mechanisms of treatment resistance and to design more effective therapeutic strategies. Conventional cancer treatments, including cytotoxic chemotherapy, radiation therapy, and targeted therapy, have immunomodulatory effects in addition to direct cancer cell-killing activities. Their clinical utilities in combination with ICIs have been explored, aiming to achieve synergetic effects with improved and durable clinical response. We will review the immunomodulatory effects of chemotherapy, targeted therapy, and radiation therapy, in the setting of ICI, and their clinical implications in reshaping modern cancer immunotherapy

INTRODUCTION
Immunomodulatory Impact of Cytotoxic Chemotherapy
Clinical Studies With CIT Combinations
Considerations and Challenges
Therapy regimes
NSCLC Urothelial Cancer
Metastatic melanoma Ipilimumab plus temozolomide
COMBINATION OF IMMUNOTHERAPY AND MOLECULAR TARGETED THERAPY
BRAF and MEK Inhibitors
Metastatic melanoma
VEGF Inhibitors
Ongoing Ongoing
Metastatic solid tumor
Metastatic renal cell carcinoma and urothelial carcinoma
Findings
CONCLUSION
Full Text
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