Clinical and Recent Patents Applications of PD-1/PD-L1 Targeting Immunotherapy in Cancer Treatment—Current Progress, Strategy, and Future Perspective

Guo, Libin; Wei, Ran; Lin, Yao; Kwok, Hang Fai

doi:10.3389/fimmu.2020.01508

Cited by 70 publications

(46 citation statements)

References 122 publications

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“…Importantly, the use of anti-PD-1 or anti-PD-L1 mAbs improves the anti-tumor activity of NK cells against PD-L1/2 + tumor cells [25,26,28,51]. This is clinically relevant for patients with tumors displaying a T-cell-resistant (i.e., HLA-I − ) phenotype.…”

Section: Sym023mentioning

confidence: 99%

“…Solid tumors, including Kaposi sarcoma, PC, ovarian and lung cancers [26][27][28][29][30], and HL [31] Use of anti-PD-1 or anti-PD-L1 improves the anti-tumor activity of NK cells against PD-L1/2+ tumor cells [25,26,31,32] ILC Decidual ILCs during pregnancy [17] Tumor-associated ILC2s (>PD-1 than circulating ILCs) [33] ILC2s and ILC3s in tumors of the gastrointestinal tract (>PD-1 than in the paralesional tissue) ILC3s in human malignant pleural effusion [30] ILC2s in colorectal cancer model [33] KIRs NK TIM-3 NK Gastric cancer [38] Lung adenocarcinoma [39] Advanced melanoma [40] Bladder cancer [38][39][40][41]…”

Section: Introductionmentioning

confidence: 99%

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Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Pesce¹,

Trabanelli

Vito

et al. 2020

Cancers

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Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies.

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Section: Sym023mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Pesce¹,

Trabanelli

Vito

et al. 2020

Cancers

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“…The generation of these M2b monocytes/Mϕ during cancer progression could be affected by immune complex formation as various factors capable of inducing M2bMϕ have been described, including immune complexes [ 27 , 28 ]. Moreover, immune complexes targeting cancer antigens have been detected in the serum of patients with various cancers [ 29 , 30 ]. Therefore, it is reasonable to postulate that as cancer progresses, serum immune complexes increase, promoting the production of M2b monocytes from quiescent monocytes.…”

Section: Discussionmentioning

confidence: 99%

Programmed Death 1 Ligand Expression in the Monocytes of Patients with Hepatocellular Carcinoma Depends on Tumor Progression

Asai

Yasuoka

Morimoto

et al. 2020

Cancers

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Monocytes (CD14+ cells) from advanced-stage hepatocellular carcinoma (HCC) patients express programmed death 1 ligand (PD-L)/PD-1 and suppress the host antitumor immune response. However, it is unclear whether cancer progression is associated with CD14+ cells. We compared CD14+ cell properties before and after cancer progression in the same HCC patients and examined their role in antitumor immunity. CD14+ cells were isolated from 15 naïve early-stage HCC patients before treatment initiation and after cancer progression to advanced stages. Although CD14+ cells from patients at early HCC stages exhibited antitumor activity in humanized murine chimera, CD14+ cells from the same patients after progression to advanced stages lacked this activity. Moreover, CD14+ cells from early HCC stages scantly expressed PD-L1 and PD-L2 and produced few cytokines, while CD14+ cells from advanced stages showed increased PD-L expression and produced IL-10 and CCL1. CD14+ cells were also isolated from five naïve advanced-stage HCC patients before treatment as well as after treatment-induced tumor regression. The CD14+ cells from patients with advanced-stage HCC expressed PD-L expressions, produced IL-10 and CCL1, and exhibited minimal tumoricidal activity. After treatment-induced tumor regression, CD14+ cells from the same patients did not express PD-Ls, failed to produce cytokines, and recovered tumoricidal activity. These results indicate that PD-L expression as well as CD14+ cell phenotype depend on the tumor stage in HCC patients. PD-L expressions of monocytes may be used as a new marker in the classification of cancer progression in HCC.

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“…Several approved antibodies targeting PD-1 or PD-L1 have been patented with good curative effect in various cancer types in clinical practices. While the current antibody therapy is facing a development bottleneck, some companies have tried to develop PD-L1 companion tests to select patients with better diagnosis potential [ 62 ].…”

Section: Potentiation Of Particle-radiation-mediated Anti-tumor Immentioning

confidence: 99%

The Potentiation of Anti-Tumor Immunity by Tumor Abolition with Alpha Particles, Protons, or Carbon Ion Radiation and Its Enforcement by Combination with Immunoadjuvants or Inhibitors of Immune Suppressor Cells and Checkpoint Molecules

Keisari

Kelson

2021

Cells

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The delivery of radiation therapy (RT) for cancer with intent to cure has been optimized and standardized over the last 80 years. Both preclinical and clinical work emphasized the observation that radiation destroys the tumor and exposes its components to the immune response in a mode that facilitates the induction of anti-tumor immunity or reinforces such a response. External beam photon radiation is the most prevalent in situ abolition treatment, and its use exposed the “abscopal effect”. Particle radiotherapy (PRT), which has been in various stages of research and development for 70 years, is today available for the treatment of patients in the form of alpha particles, proton, or carbon ion radiotherapy. Charged particle radiotherapy is based on the acceleration of charged species, such as protons or carbon-12, which deposit their energy in the treated tumor and have a higher relative biological effectiveness compared with photon radiation. In this review, we will bring evidence that alpha particles, proton, or carbon ion radiation can destroy tumors and activate specific anti-tumor immune responses. Radiation may also directly affect the distribution and function of immune cells such as T cells, regulatory T cells, and mononuclear phagocytes. Tumor abolition by radiation can trigger an immune response against the tumor. However, abolition alone rarely induces effective anti-tumor immunity resulting in systemic tumor rejection. Immunotherapy can complement abolition to reinforce the anti-tumor immunity to better eradicate residual local and metastatic tumor cells. Various methods and agents such as immunoadjuvants, suppressor cell inhibitors, or checkpoint inhibitors were used to manipulate the immune response in combination with radiation. This review deals with the manifestations of particle-mediated radiotherapy and its correlation with immunotherapy of cancer.

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Clinical and Recent Patents Applications of PD-1/PD-L1 Targeting Immunotherapy in Cancer Treatment—Current Progress, Strategy, and Future Perspective

Cited by 70 publications

References 122 publications

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes

Programmed Death 1 Ligand Expression in the Monocytes of Patients with Hepatocellular Carcinoma Depends on Tumor Progression

The Potentiation of Anti-Tumor Immunity by Tumor Abolition with Alpha Particles, Protons, or Carbon Ion Radiation and Its Enforcement by Combination with Immunoadjuvants or Inhibitors of Immune Suppressor Cells and Checkpoint Molecules

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