Lung Cancer Immunotherapy: Beyond Common Immune Checkpoints Inhibitors

Catalano, Martina; Shabani, Sonia; Venturini, Jacopo; Ottanelli, Carlotta; Voltolini, Luca; Roviello, Giandomenico

doi:10.3390/cancers14246145

Cited by 13 publications

(25 citation statements)

References 198 publications

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“…Although immunotherapy is a crucial means for lung cancer, most patients remain unresponsive to the currently approved ICI because of poor antigen presentation. 33 PDT induces ICD, accompanied by the exposure of numerous DAMPs, which facilitate the recruitment and functional maturation of APCs. 34 DAMPs include CRT as an "eat-me" signal, HMGB1 as initial step-activated DCs, and ATP as a prominent "find-me" signal.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Porphyrin Cholesterol Conjugates for Enhanced Photodynamic Immunotherapy toward Lung Cancer

Zhao

Hao

et al. 2023

ACS Appl. Mater. Interfaces

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Lung cancer is the major cause of cancer death worldwide. Immune checkpoint inhibitors (ICIs) of PD-1/PD-L1 have improved the survival rate in some patients with lung cancer. However, the efficacy of ICIs is limited by the inhibitory tumor immune microenvironment. Herein, we designed porphyrin cholesterol conjugates (TPPC) for synergistic photodynamic therapy (PDT)−immunotherapy for lung cancer. Porphyrin derivatives with great reactive oxygen species (ROS) production efficiency have been applied as photosensitizers in clinics, and cholesterol is one of the main components of the cell membrane. Porphyrin cholesterol conjugates could assemble into nanoparticles (NPs) in the absence of surfactants or amphiphilic polymers. On the other hand, TPPC NP-mediated PDT could accumulate at the tumor site and induce immunogenic cell death to stimulate and recruit antigen-presenting cells to mature and activate T cells, rendering cancer cells more sensitive to ICIs. Importantly, the combination strategy reshapes the tumor immune microenvironment to enhance the antitumor immune response and significantly suppresses the tumor growth and eliminates metastasis. This study offers theoretical guidance for the combination of PDT and ICIs as a potential therapeutic option in lung cancer.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Porphyrin Cholesterol Conjugates for Enhanced Photodynamic Immunotherapy toward Lung Cancer

Zhao

Hao

et al. 2023

ACS Appl. Mater. Interfaces

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“…Due to their key role in the regulation of T-cell responses, PD-1 and Tim-3 are known as immune checkpoint molecules [21] . Here, most CD39 + CD8 + T cells in MPE displayed the exhausted phenotype of T cells, indicative of expressing of PD-1, Tim-3.…”

Section: Discussionmentioning

confidence: 99%

CD39 identifies a specific CD8+T cell population in EGFR- driven lung adenocarcinoma related metastatic pleural effusion

Lv,

Wang,

Zhang

et al. 2023

Preprint

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Malignant pleural effusion (MPE) is common in lung cancer, which was a complex microenvironment containing a plethora of immune and tumor signals. Gene alterations such as driver gene mutations were considered to affect the components in the TIME of non-small-cell lung cancer （NSCLC）. Here, we demonstrated that pleural CD39+CD8+T cells were selectively elevated in firstly-diagnosed lung adenocarcinoma with wild-type epidermal growth factor receptor (EGFRwt) compared to that in mutant epidermal growth factor receptor (EGFRmu), while abnormally more represented in MPE with epidermal growth factor receptor-tyrosine kinase inhibitor acquired resistance (AR-EGFR-TKI). Analysis showed that pleural CD39+CD8+T cells display exhausted phenotype and potential cytolytic function, together with skewed usages of T cell receptor (TCR)-Vβ repertoire in comparison with CD39-CD8+T cells, which constituted common feature of lung adenocarcinoma related MPE. Further study revealed TCR-Vβ diversity tended to be more enhanced in pleural CD39+CD8+T cell from MPE coupled with AR-EGFR-TKI. Taken together, we have identified a subset of CD8+T cells expressing CD39 in MPE, whom proposed as the potential tumor-reactive CD8+T cells, and further provided a new understanding of dynamic immune composition of EGFR-mutant tumor microenvironment.

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“…The Phase II ARC-7 trial (NCT04262856) is currently investigating the combination of the anti-TIGIT domvanalimab and zimberelimab (an anti-PD-1 drug) on PD-L1-positive locally advanced or metastatic NSCLC patients. In addition, a phase II study (NCT 04791839) is evaluating the use of domvanalimab + zimberelimab along with etrumadenant (an adenosine receptor antagonist) in previously treated NSCLC patients [25]. A Phase III (NCT04746924) study is underway to assess the effectiveness of ociperlimab + tislelizumab, as opposed to pembrolizumab, in previously untreated patients with advanced NSCLC and PD-L1 tumor cell ≥ 50% expression [26].…”

Section: Clinical Trials In Lung Cancer Utilizing Tigit-blockadementioning

confidence: 99%

TIGIT in Lung Cancer: Potential Theranostic Implications

Pescia

Pini

Olmeda

et al. 2023

Life

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TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a co-inhibitory receptor expressed on various immune cells, including T cells, NK cells, and dendritic cells. TIGIT interacts with different ligands, such as CD155 and CD112, which are highly expressed on cancer cells, leading to the suppression of immune responses. Recent studies have highlighted the importance of TIGIT in regulating immune cell function in the tumor microenvironment and its role as a potential therapeutic target, especially in the field of lung cancer. However, the role of TIGIT in cancer development and progression remains controversial, particularly regarding the relevance of its expression both in the tumor microenvironment and on tumor cells, with prognostic and predictive implications that remain to date essentially undisclosed. Here, we provide a review of the recent advances in TIGIT-blockade in lung cancer, and also insights on TIGIT relevance as an immunohistochemical biomarker and its possible theranostic implications.

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Lung Cancer Immunotherapy: Beyond Common Immune Checkpoints Inhibitors

Cited by 13 publications

References 198 publications

Porphyrin Cholesterol Conjugates for Enhanced Photodynamic Immunotherapy toward Lung Cancer

Porphyrin Cholesterol Conjugates for Enhanced Photodynamic Immunotherapy toward Lung Cancer

CD39 identifies a specific CD8+T cell population in EGFR- driven lung adenocarcinoma related metastatic pleural effusion

TIGIT in Lung Cancer: Potential Theranostic Implications

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