Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review

Longo, Vito; Brunetti, Oronzo; Azzariti, Amalia; Galetta, Domenico; Nardulli, Patrizia; Leonetti, Francesco; Silvestris, Nicola

doi:10.3390/cancers11040539

Cited by 49 publications

(39 citation statements)

References 91 publications

(120 reference statements)

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“…However, recent studies have also focused on the potential functions of some molecules, which can modify the immune microenvironment to up-regulate the proportion of immune-activated cells and down-regulate the immune-suppressive cells to improve the efficacy of cancer immunotherapy. The drugs include microbiota modifiers, drugs targeting co-inhibitory receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses [ 113 ].…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy-Mediated Immunomodulation and Anti-Tumor Abscopal Effect Combining Immune Checkpoint Blockade

Zhao

Shao

2020

Cancers

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Radiotherapy (RT) is a conventional method for clinical treatment of local tumors, which can induce tumor-specific immune response and cause the shrinkage of primary tumor and distal metastases via mediating tumor infiltration of CD8+ T cells. Ionizing radiation (IR) induced tumor regression outside the radiation field is termed as abscopal effect. However, due to the mobilization of immunosuppressive signals by IR, the activated CD8+T cells are not sufficient to maintain a long-term positive feedback to make the tumors regress completely. Eventually, the “hot” tumors gradually turn to “cold”. With the advent of emerging immunotherapy, the combination of immune checkpoint blockade (ICB) and local RT has produced welcome changes in stubborn metastases, especially anti-PD-1/PD-L1 and anti-CTLA-4 which have been approved in clinical cancer treatment. However, the detailed mechanism of the abscopal effect induced by combined therapy is still unclear. Therefore, how to formulate a therapeutic schedule to maximize the efficacy should be took into consideration according to specific circumstance. This paper reviewed the recent research progresses in immunomodulatory effects of local radiotherapy on the tumor microenvironment, as well as the unique advantage for abscopal effect when combined with ICB, with a view to exploring the potential application value of radioimmunotherapy in clinic.

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Section: Discussionmentioning

confidence: 99%

Radiotherapy-Mediated Immunomodulation and Anti-Tumor Abscopal Effect Combining Immune Checkpoint Blockade

Zhao

Shao

2020

Cancers

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“…Despite the fact that the impact of ICIs on malignancies treatment is unprecedented, unlike melanoma and non-small cell lung cancer, the response rate in HCC remains low. in regards to this , as well as for other malignancies, researchers are evaluating combined approaches to increase the efficacy of ICIs [38].The combination of ICIs with anti-VEGF therapy is a major approach under investigation for HCC patients using the immunomodulatory effects of anti-VEGF drug as a means of decreasing CD4+ regulatory T-Lymphocytes and MDSCs as well as the activation and differentiation of dentric cells [39,40]. The combination of atezolizumab and bevacizumab resulted in 61% partial response among 21 HCC patients with a relatively positive tolerability characterized by 35% of the subjects experiencing grade III/IV adverse events [41].…”

Section: Combinatorial Approaches With Checkpoint Inhibitorsmentioning

confidence: 99%

Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Longo¹,

Brunetti²,

Gaspar³

et al. 2019

Preprint

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Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib has been the standard of care for almost a decade until 2018 when FDA approved an alternative first-line agent namely lenvatinib. Whereas FOLFOX4 results an alternative first-line treatment for the chinese clinical oncology guidelines. In addition to cabozantinib, regorafenib, and ramucirumab, two therapeutics against the PD-L1/PD1 axis have been recently approved for subsequent-line therapy, as nivolumab and pembrolizumab. However, similar to other solid tumors, the response rate of single-agent targeting PD-L1/PD1 axis is low. Therefore a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors, the addition of immune checkpoint inhibitors after resection or during locoregional therapy, immune checkpoint inhibitors in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with an attent evaluation of new ICIs based combinatory approaches.

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“…Now they are an established treatment for melanoma [ 7 , 8 ], NSCLC (non-small-cell lung carcinoma) [ 9 , 10 ], renal cell carcinoma [ 11 , 12 ], and are believed to be effective for some other cancer types [ 5 , 6 , 13 , 14 , 15 , 16 ]. Notably, it was observed that the efficacy of such therapy depends on the individual patient [ 13 , 17 , 18 ], which makes it necessary to investigate biomarkers of improved response. It is currently believed that a better response to ICIs is associated with PD-L1 expression, the number of tumor infiltrated lymphocytes, etc.…”

Section: Introductionmentioning

confidence: 99%

“…It is currently believed that a better response to ICIs is associated with PD-L1 expression, the number of tumor infiltrated lymphocytes, etc. [ 13 , 17 , 18 , 19 ]. It was also noticed that the efficacy of treatment with ICIs correlates with the tumor mutation burden (TMB) [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…Taking into account that TMB can apparently reflect the so-called neoantigen burden [ 22 , 23 , 24 ], one could conclude that these observations highlight the importance of neoantigens as a triggering factor for tumor immune response related to T-cell activation [ 25 , 26 , 27 ]. It is not surprising that TMB is now justifiably considered to be a potential biomarker of response to immune checkpoint blockade therapy on par with other, well-established biomarkers [ 13 , 17 , 18 , 19 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Main Strategies for the Identification of Neoantigens

Gopanenko

Кособокова

Косоруков

2020

Cancers

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Genetic instability of tumors leads to the appearance of numerous tumor-specific somatic mutations that could potentially result in the production of mutated peptides that are presented on the cell surface by the MHC molecules. Peptides of this kind are commonly called neoantigens. Their presence on the cell surface specifically distinguishes tumors from healthy tissues. This feature makes neoantigens a promising target for immunotherapy. The rapid evolution of high-throughput genomics and proteomics makes it possible to implement these techniques in clinical practice. In particular, they provide useful tools for the investigation of neoantigens. The most valuable genomic approach to this problem is whole-exome sequencing coupled with RNA-seq. High-throughput mass-spectrometry is another option for direct identification of MHC-bound peptides, which is capable of revealing the entire MHC-bound peptidome. Finally, structure-based predictions could significantly improve the understanding of physicochemical and structural features that affect the immunogenicity of peptides. The development of pipelines combining such tools could improve the accuracy of the peptide selection process and decrease the required time. Here we present a review of the main existing approaches to investigating the neoantigens and suggest a possible ideal pipeline that takes into account all modern trends in the context of neoantigen discovery.

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Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review

Cited by 49 publications

References 91 publications

Radiotherapy-Mediated Immunomodulation and Anti-Tumor Abscopal Effect Combining Immune Checkpoint Blockade

Radiotherapy-Mediated Immunomodulation and Anti-Tumor Abscopal Effect Combining Immune Checkpoint Blockade

Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Main Strategies for the Identification of Neoantigens

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