Recent Advances in Cancer Immunotherapy

Suda, Kenichi

doi:10.3390/biom11020335

Cited by 6 publications

(3 citation statements)

References 9 publications

(15 reference statements)

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“…Immunotherapies have experienced profound responses and unprecedented clinical benefits in many cancers, including previously terminal stages of relapsed or refractory B-cell lymphoma, advanced non-small-cell lung cancer (NSCLC), and metastatic melanoma [5,12,24,[32][33][34][35][36]. Unfortunately, the same treatment only showed modest clinical benefits in a small subset of patients with cervical cancers [8].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the immunogenomic landscape and clinical features in cervical cancer

Fan

2021

Preprint

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Immunotherapy has changed the standard of treatment for many cancers. However, the same treatments showed disappointing outcomes in cervical cancer so far. Thus, understanding the mechanisms that support the immune tolerance of cervical cancer will provide a way to design new strategies to enhance immunotherapies. Here, we characterized cellular compositions of the immune infiltrates in cervical cancer and investigated if the tumor immune landscape is a predictor for patient prognosis. The fraction of ten immune infiltrates of cervical and other cancers were analyzed by using QuanTIseq software base on the bulk mRNA sequencing data from The Cancer Genome Atlas Program (TCGA). Cervical cancer is one of the cancers that had the lowest percentage of total immune infiltrates, but it had the highest ratio for CD8 T cells to all immune infiltrates among all solid cancers. Both the principal components (PCA) analysis and heatmap with dendrogram analysis showed that cervical cancer had a similar immune infiltrated microenvironment with other squamous cell carcinomas, such as head and neck cancer and lung squamous cell cancer. The PCA and heatmap with dendrogram analysis showed that cervical cancer and HPV positive head and neck cancers were clustered more closer and partially separated with HPV negative head and neck cancer. Further analysis showed that HPV-positive cervical and head and neck cancers had a significantly higher level of CD8 T cells and M1-liked macrophages, but a lower level of M2 macrophages. The survival analysis showed that a higher level of CD8 T cells was associated with a better patient prognosis. However, immuno-suppressive immune infiltrates including M2 macrophages and Treg cells that are known to suppress anti-tumor immunity also demonstrated positive patient overall survival. Our study provided a conceptual framework to understand the tumor immune microenvironment of cervical cancer. Our results also demonstrated that the immune infiltrates can be a prognosis marker for cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the immunogenomic landscape and clinical features in cervical cancer

Fan

2021

Preprint

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“…Perioperative immune checkpoint inhibitors (ICIs) have demonstrated therapeutic advantages in various cancers by enhancing the frequency and functionality of T cells [12,13]. In this study, we investigated the impact of perioperative α-CTLA-4 combined with αPD-1 on urinary and peripheral T cells in treatment-responsive individuals versus nonresponsive patients.…”

Section: Urinary T Cell Subsets Are Significantly Increased In Patien...mentioning

confidence: 99%

Perioperative Immune Checkpoint Blockade for Muscle-Invasive and Metastatic Bladder Cancer

Ramamurthy,

Wheeler,

Trecarten

et al. 2024

J Cancer Immunol

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Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration—neoadjuvant or adjuvant—remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. In addition, a novel murine model of spontaneous metastatic bladder cancer was used to compare the efficacy of neoadjuvant versus adjuvant anti-PD-L1 (αPD-L1) treatment. The clinical trial was closed prematurely due to the industry’s withdrawal of drug provision. Adverse events were observed in all patients; however, serious adverse events were not observed in any patient. A complete pathologic response was observed in 50% of the 4 patients enrolled. Response to treatment was significantly associated with elevated urinary T cells including CD8+ and IFNγ+ CD4+ T cells, suggesting potential reinforcement of immune responses by neoadjuvant αPD-1 and αCTLA-4 against bladder tumor cells. These findings suggest that combining chemotherapy and immunotherapy in the neoadjuvant setting could be safe. However, the complete response rate of this four-drug regimen was modest and emphasizes the need for randomized controlled trials to properly assess immunotherapy efficacy in the neoadjuvant setting. In corresponding murine studies, the MB49-met model consistently displayed widespread metastasis, including tumor growth in the lungs, liver, and bowel mesentery, within 20 days of subcutaneous transplantation. Mice receiving surgery plus neoadjuvant αPD-L1 or adjuvant αPD-L1 exhibited improved survival compared to those receiving only αPD-L1. However, no significant difference in survival was observed between the neoadjuvant and adjuvant αPD-L1 cohorts. Furthermore, the timing of neoadjuvant therapy administration (early vs. late) did not significantly impact survival. This study highlights the potential of perioperative immunotherapy in the treatment of locally advanced and metastatic bladder cancer.

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“…Initially, the approval of recombinant versions of the cytokine interferon- α ushered in an era full of innovation and possibility for oncology treatment in 1986 1 . Then the following decades witnessed numerous advances and setbacks during the development of immunotherapy, especially the emergence of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapies, which were highlighted as milestones for cancer immunotherapy despite nonnegligible adverse effects 1 , 2 , 3 , 4 . To date, dozens of cancer immunotherapies, such as durvalumab 5 , tisagenlecleucel 6 , and axicabtagene ciloleucel 7 , have been approved by the medical products administration.…”

Section: Introductionmentioning

confidence: 99%

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Xiong

Sun

et al. 2022

Acta Pharmaceutica Sinica B

114

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Recent Advances in Cancer Immunotherapy

Abstract: The strategy to use the immune system to fight cancer is not a novel concept; in 1891, Coley reported the treatment of three cases of sarcoma by inoculation with erysipelas [1] [...]

Cited by 6 publications

References 9 publications

Comprehensive analysis of the immunogenomic landscape and clinical features in cervical cancer

Comprehensive analysis of the immunogenomic landscape and clinical features in cervical cancer

Perioperative Immune Checkpoint Blockade for Muscle-Invasive and Metastatic Bladder Cancer

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

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