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In Vivo Biomarkers for Immunotherapy Efficacy in Brain Tumours
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In Vivo Biomarkers for Immunotherapy Efficacy in Brain Tumours

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 10635

Special Issue Editor

Prof. Dr. Ana Paula Candiota

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Guest Editor
Centro de Investigación Biomédica en Red: Bioingeniería, Biomateriales y Nanomedicina, Departament de Bioquímica i Biologia Molecular, Facultat de Ciències/Biociències, Edifici Cs Campus UAB, 08193 Cerdanyola del Vallès, Spain
Interests: magnetic resonance spectroscopy; imaging biomarkers; preclinical tumour models; MR contrast agents; brain tumours; magnetic resonance imaging
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Special Issue Information

Dear Colleagues,

Immunotherapy, in a broad sense, is gaining ground in cancer treatment and recent literature suggests that brain tumours could also benefit from such strategies. However, we still lack early in vivo biomarkers of successful immunotherapy or, in other words, biomarkers signaling effective immune system recruitment and action against tumours. The well-known pseudoprogression and pseudoresponse phenomena can lead to a misinterpretation at follow-up of the in vivo response to therapy in brain tumours. Moreover, since repeated biopsy is not feasible in human patients and not all patients will benefit from these therapies, knowing in advance whether an immunotherapy is properly recruiting the immune system or not would be of great benefit to patient management. In this Special Issue, we invite researchers to submit original research articles or reviews covering different aspects of the development, validation, and evaluation of in vivo biomarkers of immunotherapy. Potential topics include, but are not limited to imaging biomarkers based on MR approaches or PET; biomarker validation; liquid biopsies; preclinical studies that unravel cellular/molecular aspects of the response to immunotherapy.

Prof. Dr. Ana Paula Candiota
Guest Editor

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Published Papers (3 papers)

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24 pages, 4340 KiB  
Review
Physiological Imaging Methods for Evaluating Response to Immunotherapies in Glioblastomas
by Sanjeev Chawla, Vanessa Shehu, Pradeep K. Gupta, Kavindra Nath and Harish Poptani
Int. J. Mol. Sci. 2021, 22(8), 3867; https://doi.org/10.3390/ijms22083867 - 8 Apr 2021
Cited by 14 | Viewed by 3702
Abstract
Glioblastoma (GBM) is the most malignant brain tumor in adults, with a dismal prognosis despite aggressive multi-modal therapy. Immunotherapy is currently being evaluated as an alternate treatment modality for recurrent GBMs in clinical trials. These immunotherapeutic approaches harness the patient’s immune response to [...] Read more.
Glioblastoma (GBM) is the most malignant brain tumor in adults, with a dismal prognosis despite aggressive multi-modal therapy. Immunotherapy is currently being evaluated as an alternate treatment modality for recurrent GBMs in clinical trials. These immunotherapeutic approaches harness the patient’s immune response to fight and eliminate tumor cells. Standard MR imaging is not adequate for response assessment to immunotherapy in GBM patients even after using refined response assessment criteria secondary to amplified immune response. Thus, there is an urgent need for the development of effective and alternative neuroimaging techniques for accurate response assessment. To this end, some groups have reported the potential of diffusion and perfusion MR imaging and amino acid-based positron emission tomography techniques in evaluating treatment response to different immunotherapeutic regimens in GBMs. The main goal of these techniques is to provide definitive metrics of treatment response at earlier time points for making informed decisions on future therapeutic interventions. This review provides an overview of available immunotherapeutic approaches used to treat GBMs. It discusses the limitations of conventional imaging and potential utilities of physiologic imaging techniques in the response assessment to immunotherapies. It also describes challenges associated with these imaging methods and potential solutions to avoid them. Full article
(This article belongs to the Special Issue In Vivo Biomarkers for Immunotherapy Efficacy in Brain Tumours)
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24 pages, 3385 KiB  
Article
Anti-PD-1 Immunotherapy in Preclinical GL261 Glioblastoma: Influence of Therapeutic Parameters and Non-Invasive Response Biomarker Assessment with MRSI-Based Approaches
by Shuang Wu, Pilar Calero-Pérez, Carles Arús and Ana Paula Candiota
Int. J. Mol. Sci. 2020, 21(22), 8775; https://doi.org/10.3390/ijms21228775 - 20 Nov 2020
Cited by 16 | Viewed by 3455
Abstract
Glioblastomas (GBs) are malignant brain tumours with poor prognosis even after aggressive therapy. Programmed cell death-1 (PD-1) immune checkpoint blockade is a promising strategy in many types of cancer, but its therapeutic effects in GB remain low and associated with immune infiltration. Previous [...] Read more.
Glioblastomas (GBs) are malignant brain tumours with poor prognosis even after aggressive therapy. Programmed cell death-1 (PD-1) immune checkpoint blockade is a promising strategy in many types of cancer, but its therapeutic effects in GB remain low and associated with immune infiltration. Previous work suggests that oscillations of magnetic resonance spectroscopic imaging (MRSI)-based response pattern with chemotherapy could act as a biomarker of efficient immune system attack onto GBs. The presence of such oscillations with other monotherapies such as anti-PD-1 would reinforce its monitoring potential. Here, we confirm that the oscillatory behaviour of the response biomarker is also detected in mice treated with anti PD-1 immunotherapy both in combination with temozolomide and as monotherapy. This indicates that the spectral pattern changes observed during therapy response are shared by different therapeutic strategies, provided the host immune system is elicited and able to productively attack tumour cells. Moreover, the participation of the immune system in response is also supported by the rate of cured animals observed with different therapeutic strategies (in the range of 50–100% depending on the treatment), which also held long-term immune memory against tumour cells re-challenge. Taken together, our findings open the way for a translational use of the MRSI-based biomarker in patient-tailored GB therapy, including immunotherapy, for which reliable non-invasive biomarkers are still missing. Full article
(This article belongs to the Special Issue In Vivo Biomarkers for Immunotherapy Efficacy in Brain Tumours)
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19 pages, 6128 KiB  
Article
Upregulation of the APOBEC3 Family Is Associated with a Poor Prognosis and Influences Treatment Response to Raf Inhibitors in Low Grade Glioma
by Cheng Luo, Songmao Wang, Weijie Liao, Shikuan Zhang, Naihan Xu, Weidong Xie and Yaou Zhang
Int. J. Mol. Sci. 2021, 22(19), 10390; https://doi.org/10.3390/ijms221910390 - 27 Sep 2021
Cited by 5 | Viewed by 2705
Abstract
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) has been identified as a group of enzymes that catalyze cytosine deamination in single-stranded (ss) DNA to form uracil, causing somatic mutations in some cancers. We analyzed the APOBEC3 family in 33 TCGA cancer types [...] Read more.
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) has been identified as a group of enzymes that catalyze cytosine deamination in single-stranded (ss) DNA to form uracil, causing somatic mutations in some cancers. We analyzed the APOBEC3 family in 33 TCGA cancer types and the results indicated that APOBEC3s are upregulated in multiple cancers and strongly correlate with prognosis, particularly in low grade glioma (LGG). Then we constructed a prognostic model based on family expression in LGG where the APOBEC3 family signature is an accurate predictive model (AUC of 0.85). Gene mutation, copy number variation (CNV), and a differential gene expression (DEG) analysis were performed in different risk groups, and the weighted gene co-expression network analysis (WGCNA) was employed to clarify the role of various members in LGG; CIBERSORT algorithm was deployed to evaluate the landscape of LGG immune infiltration. We found that upregulation of the APOBEC3 family expression can strengthen Ras/MAPK signaling pathway, promote tumor progression, and ultimately reduce the treatment benefits of Raf inhibitors. Moreover, the APOBEC3 family was shown to enhance the immune response mediated by myeloid cells and interferon gamma, as well as PD-L1 and PD-L2 expression, implying that they have immunotherapy potential. Therefore, the APOBEC3 signature enables an efficient assessment of LGG patient survival outcomes and expansion of clinical benefits by selecting appropriate individualized treatment strategies. Full article
(This article belongs to the Special Issue In Vivo Biomarkers for Immunotherapy Efficacy in Brain Tumours)
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