International Journal of Molecular Sciences

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Immunotherapy: New Developments and Challenges

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Dear Colleagues,

Immunotherapy is a promising strategy for cancer treatment that harnesses the power of the immune system to fight tumor cells. However, current immunotherapeutic agents have limitations such as high toxicity, low specificity, and poor bioavailability.

The most successful cancer therapies are immune checkpoint inhibitors (ICIs), bi-specific T-cell engagers (BiTEs), and chimeric antigen receptor T cells (CAR-T cells). The possibility for a combination therapy built on the aforementioned techniques has recently been considered by researchers and has been demonstrated to have a significantly stronger impact on cancer therapy. Therefore, new research methodologies are necessary for a full explanation of the processes behind various cancer therapeutic approaches.

This Special Issue aims to publish original research papers, systematic reviews, and opinion pieces that focus on clinical/translational cancer immunotherapy, covering both in vitro and in vivo experiments on new immunotherapeutic strategies, therapy-related immune regulation, and immunotherapy markers.

Dr. Xingxing Fan
Dr. Paolo Coghi
Guest Editors

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Keywords

tumor microenvironment
small molecules
IDO1 inhibition
checkpoint inhibitor therapy
adoptive T cell therapy
metabolic reprogram
resistance mechanisms
immune modulation
immune reconstitution
combination therapy
immunosuppression

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18 pages, 13605 KiB

Open AccessArticle

The Transcriptional Landscape of Immune-Response 3′-UTR Alternative Polyadenylation in Melanoma

by Xiao Yang, Yingyi Wu, Xingyu Chen, Jiayue Qiu and Chen Huang

Int. J. Mol. Sci. 2024, 25(5), 3041; https://doi.org/10.3390/ijms25053041 - 06 Mar 2024

Viewed by 714

Abstract

The prognosis of patients with malignant melanoma has been improved in recent decades due to advancements in immunotherapy. However, a considerable proportion of patients are refractory to treatment, particularly at advanced stages. This underscores the necessity of developing a new strategy to improve it. Alternative polyadenylation (APA), as a marker of crucial posttranscriptional regulation, has emerged as a major new type of epigenetic marker involved in tumorigenesis. However, the potential roles of APA in shaping the tumor microenvironment (TME) are largely unexplored. Herein, we collected two cohorts comprising melanoma patients who received immune checkpoint inhibitor (ICI) immunotherapy to quantify transcriptome-wide discrepancies in APA. We observed a global change in 3′-UTRs between responders and non-responders, which might involve DNA damage response, angiogenesis, PI3K-AKT signaling pathways, etc. Ten putative master APA regulatory factors for those APA events were detected via a network analysis. Notably, we established an immune response-related APA scoring system (IRAPAss), which exhibited a great performance of predicting immunotherapy response in multiple cohorts. Furthermore, we examined the correlation of APA with TME at the single-cell level using four single-cell immune profiles of tumor-infiltrating lymphocytes (TILs), which revealed an overall discrepancy in 3′-UTR length across diverse T cell populations, probably contributing to immunoregulation in melanoma. In conclusion, our study provides a transcriptional landscape of APA implicated in immunoregulation, which might lay the foundation for developing a new strategy for improving immunotherapy response for melanoma patients by targeting APA. Full article

(This article belongs to the Special Issue Immunotherapy: New Developments and Challenges)

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Immunotherapy: New Developments and Challenges

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