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A comprehensive insights of cancer immunotherapy resistance.

Med Oncol

January 2025

Department of In Vivo Pharmacology, TCG Lifesciences Pvt. Ltd, BN 7, Sector V, Salt Lake City, Kolkata, West Bengal, 700091, India.

Cancer is a major global health issue that is usually treated with multiple therapies, such as chemotherapy and targeted therapies like immunotherapy. Immunotherapy is a new and alternative approach to treating various types of cancer that are difficult to treat with other methods. Although immune checkpoint inhibitors have shown promise for long-term efficacy, they have limited effectiveness in common cancer types such as breast, prostate, and lung.

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Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant tumor of the liver and gallbladder, which is usually diagnosed at an advanced stage and the opportunity for surgery is lost. Therefore, conversion therapy is important to convert the iCCA into a resectable state. In recent years, the conversion protocol of immuno-chemotherapy has been applied for advanced liver cancer.

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PD-L1/PD-1 checkpoint inhibitors (CPIs) are mainstream agents for cancer immunotherapy, but the prognosis is unsatisfactory in solid tumor patients lacking preexisting T-cell reactivity. Adjunct therapy strategies including the intratumoral administration of immunostimulants aim to address this limitation. CpG oligodeoxynucleotides (ODNs), TLR9 agonists that can potentiate adaptive immunity, have been widely investigated to tackle PD-L1/PD-1 resistance, but clinical success has been hindered by inconsistent efficacy and immune-related toxicities caused by systemic exposure.

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Glioblastoma multiforme (GBM) is a tumor with a high refractory rate to immunotherapy and a low tumor mutational burden phenotype, leading to limited immunogenic neoantigens. The present study aimed to investigate the sequential use of immunotherapy and bevacizumab in patients with GBM, exploring the clinical outcomes and potential complications. Patients received various combinations of immunotherapy and bevacizumab after standard treatment, including surgery, radiotherapy and temozolomide.

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Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).

Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.

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