Obstacles for T-lymphocytes in the tumour microenvironment: Therapeutic challenges, advances and opportunities beyond immune checkpoint

Verma, Navin Kumar; Wong, Brandon Han Siang; Poh, Zhi Sheng; Udayakumar, Aiswarya; Verma, Ritu; Goh, Ryan Kwang Jin; Duggan, Shane P.; Shelat, Vishal G; Chandy, K. George; Grigoropoulos, Nicholas F.

doi:10.1016/j.ebiom.2022.104216

Cited by 58 publications

(49 citation statements)

References 73 publications

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“…Secondly, this study had a small sample size; thus, a large sample size and prospective studies are still needed for validation. Moreover, the tumor microenvironment could affect the function of T-lymphocytes, which might affect the results of this study [ 39 ]. Finally, the constructed nomograms in this study were only applied to cases of unresectable HCC patients who underwent TACE, and it is unclear whether they are applicable to predict the prognosis of other HCC patients.…”

Section: Discussionmentioning

confidence: 99%

PNI-Based Nomograms to Predict Tumor Progression and Survival for Patients with Unresectable Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization

Lei

Deng

Wang

et al. 2023

JCM

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Background: The relationship between the prognostic nutritional index (PNI) and the prognosis of malignancy has been increasingly mentioned in recent research. This study aimed to construct nomograms based on the PNI to predict tumor progression and survival in patients with unresectable hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE). Materials and Methods: The development set included 785 patients who underwent their first TACE between 2012 and 2016, and the validation set included 336 patients who underwent their first TACE between 2017 and 2018. The clinical outcomes included the time to progression (TTP) and overall survival (OS). Cox regression was applied to screen for independent risk factors of TTP and OS in the development set, and PNI-based nomograms were constructed for TTP and OS. The predictive performance of nomograms was conducted through the C-index, calibration curves, and decision analysis curves in the development set and validation set. Results: After multivariate analysis, the prognostic predictors of both TTP and OS included portal vessel invasion, extrahepatic metastasis, tumor number, alpha-fetoprotein (AFP) level, longest tumor diameter, and PNI. Furthermore, the Child–Pugh classification and platelets (PLTs) were independent risk factors for OS only. Nomograms for predicting TTP and OS were constructed using TTP and OS prognostic factors. In the development set and the validation set, the C-index of the TTP nomograms was 0.699 (95% confidence interval (CI): 0.680–0.718) and 0.670 (95%CI: 0.638–0.702), and the C-index of the OS nomograms was 0.730 (95%CI: 0.712–0.748) and 0.700 (95%CI: 0.665–0.723), respectively. Conclusion: Nomograms based on the PNI can effectively predict tumor progression and survival in patients with unresectable HCC undergoing TACE.

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Section: Discussionmentioning

confidence: 99%

PNI-Based Nomograms to Predict Tumor Progression and Survival for Patients with Unresectable Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization

Lei

Deng

Wang

et al. 2023

JCM

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“…One of the most critical responses of lymphocytes related to the TME is cytotoxicity, mainly regulated by T CD8 + and natural killers ( 128 ). Natural killers are known for expressing CD16, which recognizes tumor cells and causes antibody-dependence cell cytotoxicity ( 129 ).…”

Section: Organs On a Chip For Solid Tumors-adaptive Immune System Int...mentioning

confidence: 99%

Opportunities and challenges to engineer 3D models of tumor-adaptive immune interactions

et al. 2023

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Augmenting adaptive immunity is a critical goal for developing next-generation cancer therapies. T and B cells infiltrating the tumor dramatically influence cancer progression through complex interactions with the local microenvironment. Cancer cells evade and limit these immune responses by hijacking normal immunologic pathways. Current experimental models using conventional primary cells, cell lines, or animals have limitations for studying cancer-immune interactions directly relevant to human biology and clinical translation. Therefore, engineering methods to emulate such interplay at local and systemic levels are crucial to expedite the development of better therapies and diagnostic tools. In this review, we discuss the challenges, recent advances, and future directions toward engineering the tumor-immune microenvironment (TME), including key elements of adaptive immunity. We first offer an overview of the recent research that has advanced our understanding of the role of the adaptive immune system in the tumor microenvironment. Next, we discuss recent developments in 3D in-vitro models and engineering approaches that have been used to study the interaction of cancer and stromal cells with B and T lymphocytes. We summarize recent advancement in 3D bioengineering and discuss the need for 3D tumor models that better incorporate elements of the complex interplay of adaptive immunity and the tumor microenvironment. Finally, we provide a perspective on current challenges and future directions for modeling cancer-immune interactions aimed at identifying new biological targets for diagnostics and therapeutics.

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“…These factors can also inactivate lymphocytes in the TME, namely NK cells and CD8 T lymphocytes, thus preventing them from combating tumor growth. In this pathway, proinflammatory signals produced in hypoxic regions of the TME attract regulatory T cells (Tregs), which in turn suppress cytotoxic T cells from producing an immune response, thus promoting cancer growth [11]. The hypoxic conditions also act as a stressor on neutrophils and block them from attacking tumors.…”

Section: Changes To Conditions Of the Tmementioning

confidence: 99%

Perspective Chapter: Impact of Tumor Metabolism on Immune Cells in the Tumor Microenvironment

Kotha¹,

Madu²,

Lu³

2023

Tumor Microenvironment - New Insights

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Metabolism is essential for a cell to obtain energy for its growth and development. In tumors, the rapid rate of cell proliferation leads to an increased demand for energy. Because nutrients in the tumor microenvironment are scarce, there is great competition between tumor cells and healthy cells to obtain them. Because of this, tumor cells undergo adaptations to outcompete healthy cells for nutrients. These adaptations cause characteristic changes to the tumor microenvironment, which in turn, causes changes to immune cells in the tumor tissue. These changes help the tumor evade immune detection and cause tumor growth and metastasis. This review will analyze the changes that take place in the tumor microenvironment, the impact they have on immune cells, and how this contributes to cancer progression.

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Obstacles for T-lymphocytes in the tumour microenvironment: Therapeutic challenges, advances and opportunities beyond immune checkpoint

Cited by 58 publications

References 73 publications

PNI-Based Nomograms to Predict Tumor Progression and Survival for Patients with Unresectable Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization

PNI-Based Nomograms to Predict Tumor Progression and Survival for Patients with Unresectable Hepatocellular Carcinoma Undergoing Transcatheter Arterial Chemoembolization

Opportunities and challenges to engineer 3D models of tumor-adaptive immune interactions

Perspective Chapter: Impact of Tumor Metabolism on Immune Cells in the Tumor Microenvironment

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