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Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment.

ABSTRACT: Advances in cancer immunity have promoted a major breakthrough in the field of cancer therapy. This is mainly associated with the successful development of immune checkpoint inhibitors (ICIs) for multiple types of human tumors. Blockade with different ICIs, including programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, may activate the immune system of the host against malignant cells. However, only a subgroup of patients with cancer would benefit from immune checkpoint blockade. Some patients experience primary resistance to initial immunotherapy, and a majority eventually develop acquired resistance to ICIs. However, the mechanisms involved in the development of drug resistance to immune checkpoint blockade remain unclear. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for overcoming the low efficacy of ICIs. Moreover, through their direct anti-cancer effect by inhibiting tumor growth and metastasis, anti-angiogenic drugs reprogram the tumor milieu from an immunosuppressive to an immune permissive microenvironment. Activated immunity by immune checkpoint blockade also facilitates anti-angiogenesis by downregulating the expression of vascular endothelial growth factor and alleviating hypoxia condition. Many clinical trials showed an improved anti-cancer efficacy and prolonged survival following the addition of anti-angiogenic agents to ICIs. This review summarizes the current understanding and clinical development of combination therapy with immune checkpoint blockade and anti-angiogenic strategy.

SUBMITTER: Song Y

PROVIDER: S-EPMC7477085 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment.

Song Yuxiao Y Fu Yang Y Xie Qi Q Zhu Bo B Wang Jun J Zhang Bicheng B

Frontiers in immunology 20200825

Advances in cancer immunity have promoted a major breakthrough in the field of cancer therapy. This is mainly associated with the successful development of immune checkpoint inhibitors (ICIs) for multiple types of human tumors. Blockade with different ICIs, including programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, may activate the immune system of the host against malignant cells. However, only a subgrou ...[more]

PMID: 32983126

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Project description:BackgroundThe combination of immune checkpoint inhibitors (ICIs) and anti-angiogenic agents has shown promising efficacy in unresectable hepatocellular carcinoma (HCC), but until now no clinical prognostic models or predictive biomarkers have been established.MethodsFrom 2016 to 2021, a total of 258 HCCs treated with ICIs and tyrosine kinase inhibitors (TKIs) were retrospectively enrolled, as the study cohort. Patients' baseline data was extracted by least absolute and shrinkage selection operator (LASSO) and Cox regression. Finally, a prognostic model in the form of nomogram was developed. Model performance was assessed in terms of discrimination, calibration, and clinical utility. A 5-fold cross-validation was used to evaluate the internal repeatability of the model. In addition, the patient cohort was divided into three subgroups according to nomogram scores. Their survivals were estimated by Kaplan-Meier methods and the differences were analyzed using log-rank tests.ResultsSeven clinical parameters were selected: Eastern Cooperative Oncology Group performance status (ECOG PS), combination of transarterial chemoembolization (TACE), extrahepatic metastasis (EHM), platelet to lymphocyte ratio (PLR), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), and Child-Pugh score. The model had an area under the curve (AUC) of 0.777 at 1 year and 0.772 at 2 years. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) showed that the discrimination, consistency and applicability of the model were good. In addition, cross-validation validated the discrimination of the model, and the C index value of the model is 0.7405. The median overall survival (OS) of the high-, medium- and low-risk subgroups was 7.58, 17.50 and 53.17 months, respectively, with a significant difference between the groups (P < 0.0001).ConclusionWe developed a comprehensive and simple prognostic model for the combination of ICIs plus TKIs. And it may predict the efficacy of the combination regimen for unresectable HCC.

Project description:Immunotherapy has emerged as the fifth pillar of cancer treatment alongside surgery, radiotherapy, chemotherapy, and targeted therapy. Immune checkpoint inhibitors are the current superheroes of immunotherapy, unleashing a patient's own immune cells to kill tumors and revolutionizing cancer treatment in a variety of cancers. Although breast cancer was historically believed to be immunologically silent, treatment with immune checkpoint inhibitors has been shown to induce modest responses in metastatic breast cancer. Given the inherent heterogeneity of breast tumors, this raised the question whether certain breast tumors might benefit more from immune-based interventions and which cancer cell-intrinsic and/or microenvironmental factors define the likelihood of inducing a potent and durable anti-tumor immune response. In this review, we will focus on triple negative breast cancer as immunogenic breast cancer subtype, and specifically discuss the relevance of tumor mutational burden, the plethora and diversity of tumor infiltrating immune cells in addition to the immunoscore, the presence of immune checkpoint expression, and the microbiome in defining immune checkpoint blockade response. We will highlight the current immune checkpoint inhibitor treatment options, either as monotherapy or in combination with standard-of-care treatment modalities such as chemotherapy and targeted therapy. In addition, we will look into the potential of immunotherapy-based combination strategies using immune checkpoint inhibitors to enhance both innate and adaptive immune responses, or to establish a more immune favorable environment for cancer vaccines. Finally, the review will address the need for unambiguous predictive biomarkers as one of the main challenges of immune checkpoint blockade. To conclude, the potential of immune checkpoint blockade for triple negative breast cancer treatment could be enhanced by exploration of aforementioned factors and treatment strategies thereby providing promising future prospects.

Dataset Information

Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment.

Publications

Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment.

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