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Cancers
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Microbiome-Based Interventions in Cancer Immunotherapy
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Microbiome-Based Interventions in Cancer Immunotherapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 24061

Special Issue Editor

Dr. Saman Maleki Vareki

E-Mail Website
Guest Editor
1. Department of Pathology and Laboratory Medicine, University of Western Ontario, London, ON N6A 3K7, Canada
2. London Regional Cancer Program, Lawson Health Research Institute, London, ON N6A 5W9, Canada
Interests: immunotherapy; microbiome; melanoma; RCC; T cells; immune-related adverse events; fecal microbiota transplant

Special Issue Information

Dear Colleagues,

Recent landmark discoveries revealed the role of the gut microbiome as a tumor-extrinsic factor in modulating antitumor immunity and affecting clinical response to immune checkpoint blockade (ICB) in cancer patients. These findings featured the gut microbiome as a potential biomarker for response to ICB treatment. Moreover, responder-derived fecal microbiota transplantation (FMT) sensitized antiprogrammed death 1 (PD1)-refractory melanoma tumors to immunotherapy. The challenge facing researchers in this fast-growing area is pinpointing the underlying mechanisms of action of the microorganisms living along barrier tissues and how they interact with the host and tumor cells that can affect a cancer patient’s response to drugs that modulate the immune system. Moreover, it is now crucial to understand how different microbial signatures can be used as biomarkers of response and toxicity in the area of immunotherapy.

We are pleased to invite you to submit research, commandry, or review articles from your work that describe the role of the gut or tumor microbiome in modulating antitumor immunity and response to immunotherapy. Your article can be in the area of therapeutics, diagnostics, biomarker, or mechanistic studies about the effect of microbiome and microorganisms on antitumor immunity.

This Special Issue aims to gather novel data or perspectives in the area of oncomicrobiome and how microbiome-based strategies can be used to 1) select potential responders to immunotherapy, 2) modulate patients’ response to these drugs, and 3) prevent toxicity in patients receiving immunotherapy.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  1. Role of microbiome in systemic and local cancer treatments;
  2. The effect of the gut and tumor microbiome on response to immunotherapy with checkpoint inhibitors or adoptive cell therapy;
  3. The role of microbiome on inducing or preventing immune-related toxicities from immunotherapy;
  4. Mechanisms of immune modulation by gut microbiome or their products;
  5. Microbiome-based biomarker strategies for patients receiving cancer immunotherapy;
  6. Microbiome-based combination therapies in the area of cancer immunotherapy.

I look forward to receiving your contributions.

Dr. Saman Maleki Vareki
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microbiome
  • microbiota
  • cancer
  • immunotherapy
  • immune checkpoint blockade
  • toxicity
  • immune-related adverse events
  • biomarker
  • metabolites

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Published Papers (6 papers)

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Research

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13 pages, 2555 KiB  
Article
Cancer Cachexia among Patients with Advanced Non-Small-Cell Lung Cancer on Immunotherapy: An Observational Study with Exploratory Gut Microbiota Analysis
by Taiki Hakozaki, Alexis Nolin-Lapalme, Masato Kogawa, Yusuke Okuma, Shohei Nakamura, Danielle Moreau-Amaru, Taichi Tamura, Yukio Hosomi, Haruko Takeyama, Corentin Richard, Masahito Hosokawa and Bertrand Routy
Cancers 2022, 14(21), 5405; https://doi.org/10.3390/cancers14215405 - 2 Nov 2022
Cited by 22 | Viewed by 4448
Abstract
Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the [...] Read more.
Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the response to ICI therapy in cancer patients. However, the association between cancer cachexia and GM and their association with the response to ICIs remains unexplored. This study examined the association of cancer cachexia with GM composition and assessed the impact of GM on clinical outcomes in patients with NSCLC treated with ICIs. In this observational, prospective study, which included 113 Japanese patients with advanced NSCLC treated with ICIs, the prevalence of cachexia was 50.4% (57/113). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group than in the non-cachexia group (4.3 vs. 11.6 months (p = 0.003) and 12.0 months vs. not reached (p = 0.02), respectively). A multivariable analysis revealed that baseline cachexia was independently associated with a shorter PFS. Moreover, a gain in body weight from the baseline (reversible cachexia) was associated with a significantly longer PFS and OS compared to irreversible cachexia. Microbiome profiling with 16S rRNA analysis revealed that the cachexia group presented an overrepresentation of the commensal bacteria, Escherichia-Shigella and Hungatella, while the non-cachexia group had a preponderance of Anaerostipes, Blautia, and Eubacterium ventriosum. Anaerostipes and E. ventriosum were associated with longer PFS and OS. Moreover, a cachexia status correlated with the systemic inflammatory marker-derived-neutrophil-to-lymphocytes ratio (dNLR) and Lung Immune Prognostic Index (LIPI) indexes. Our study demonstrates that cachexia and longitudinal bodyweight change have a prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, our study demonstrates that bacteria associated with ICI resistance are also linked to cachexia. Targeted microbiota interventions may represent a new type of treatment to overcome cachexia in patients with NSCLC. Full article
(This article belongs to the Special Issue Microbiome-Based Interventions in Cancer Immunotherapy)
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23 pages, 2263 KiB  
Article
A Clinical Outcome of the Anti-PD-1 Therapy of Melanoma in Polish Patients Is Mediated by Population-Specific Gut Microbiome Composition
by Bernadeta Pietrzak, Katarzyna Tomela, Agnieszka Olejnik-Schmidt, Łukasz Galus, Jacek Mackiewicz, Mariusz Kaczmarek, Andrzej Mackiewicz and Marcin Schmidt
Cancers 2022, 14(21), 5369; https://doi.org/10.3390/cancers14215369 - 31 Oct 2022
Cited by 10 | Viewed by 3076
Abstract
The gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between the response to anti-PD-1 therapy and the baseline gut microbiome in a Polish cohort of melanoma patients, alongside selected agents modifying [...] Read more.
The gut microbiota is considered a key player modulating the efficacy of immune checkpoint inhibitor therapy. The study investigated the association between the response to anti-PD-1 therapy and the baseline gut microbiome in a Polish cohort of melanoma patients, alongside selected agents modifying the microbiome. Sixty-four melanoma patients enrolled for the anti-PD-1 therapy, and ten healthy subjects were recruited. The response to the treatment was assessed according to the response evaluation criteria in solid tumors, and patients were classified as responders or non-responders. The association between selected extrinsic factors and response was investigated using questionnaire-based analysis and the metataxonomics of the microbiota. In the responders, the Bacteroidota to Firmicutes ratio was higher, and the richness was decreased. The abundance of Prevotella copri and Bacteroides uniformis was related to the response, whereas the non-responders’ gut microbiota was enriched with Faecalibacterium prausnitzii and Desulfovibrio intestinalis and some unclassified Firmicutes. Dietary patterns, including plant, dairy, and fat consumption as well as gastrointestinal tract functioning were significantly associated with the therapeutic effects of the therapy. The specific gut microbiota along with diet were found to be associated with the response to the therapy in the population of melanoma patients. Full article
(This article belongs to the Special Issue Microbiome-Based Interventions in Cancer Immunotherapy)
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Review

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18 pages, 1106 KiB  
Review
The Prospect of Harnessing the Microbiome to Improve Immunotherapeutic Response in Pancreatic Cancer
by Sherise Rogers, Angel Charles and Ryan M. Thomas
Cancers 2023, 15(24), 5708; https://doi.org/10.3390/cancers15245708 - 5 Dec 2023
Cited by 3 | Viewed by 2012
Abstract
Pancreatic ductal adenocarcinoma cancer (PDAC) is projected to become the second leading cause of cancer-related death in the United States by 2030. Patients are often diagnosed with advanced disease, which explains the dismal 5-year median overall survival rate of ~12%. Immunotherapy has been [...] Read more.
Pancreatic ductal adenocarcinoma cancer (PDAC) is projected to become the second leading cause of cancer-related death in the United States by 2030. Patients are often diagnosed with advanced disease, which explains the dismal 5-year median overall survival rate of ~12%. Immunotherapy has been successful in improving outcomes in the past decade for a variety of malignancies, including gastrointestinal cancers. However, PDAC is historically an immunologically “cold” tumor, one with an immunosuppressive environment and with restricted entry of immune cells that have limited the success of immunotherapy in these tumors. The microbiome, the intricate community of microorganisms present on and within humans, has been shown to contribute to many cancers, including PDAC. Recently, its role in tumor immunology and response to immunotherapy has generated much interest. Herein, the current state of the interaction of the microbiome and immunotherapy in PDAC is discussed with a focus on needed areas of study in order to harness the immune system to combat pancreatic cancer. Full article
(This article belongs to the Special Issue Microbiome-Based Interventions in Cancer Immunotherapy)
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25 pages, 5231 KiB  
Review
The Role of Microbiota-Derived Vitamins in Immune Homeostasis and Enhancing Cancer Immunotherapy
by Hasti Gholami, John A. Chmiel, Jeremy P. Burton and Saman Maleki Vareki
Cancers 2023, 15(4), 1300; https://doi.org/10.3390/cancers15041300 - 18 Feb 2023
Cited by 10 | Viewed by 4104
Abstract
Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions to the immune response have been postulated, one likely function is the supply of basic [...] Read more.
Not all cancer patients who receive immunotherapy respond positively and emerging evidence suggests that the gut microbiota may be linked to treatment efficacy. Though mechanisms of microbial contributions to the immune response have been postulated, one likely function is the supply of basic co-factors to the host including selected vitamins. Bacteria, fungi, and plants can produce their own vitamins, whereas humans primarily obtain vitamins from exogenous sources, yet despite the significance of microbial-derived vitamins as crucial immune system modulators, the microbiota is an overlooked source of these nutrients in humans. Microbial-derived vitamins are often shared by gut bacteria, stabilizing bioenergetic pathways amongst microbial communities. Compositional changes in gut microbiota can affect metabolic pathways that alter immune function. Similarly, the immune system plays a pivotal role in maintaining the gut microbiota, which parenthetically affects vitamin biosynthesis. Here we elucidate the immune-interactive mechanisms underlying the effects of these microbially derived vitamins and how they can potentially enhance the activity of immunotherapies in cancer. Full article
(This article belongs to the Special Issue Microbiome-Based Interventions in Cancer Immunotherapy)
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25 pages, 749 KiB  
Review
Monitoring and Modulating Diet and Gut Microbes to Enhance Response and Reduce Toxicity to Cancer Treatment
by Anne Knisely, Yongwoo David Seo, Jennifer A. Wargo and Manoj Chelvanambi
Cancers 2023, 15(3), 777; https://doi.org/10.3390/cancers15030777 - 27 Jan 2023
Cited by 5 | Viewed by 3595
Abstract
The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes [...] Read more.
The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can be modulated through strategies, such as fecal transplant. We also summarize the current literature that implicate high fiber and ketogenic diets in improved response rates to immunotherapy and chemotherapy, respectively. Finally, we discuss the relevance of these findings in the context of patient care, advocate for a holistic approach to cancer treatment, and comment on the next frontier of targeted gut and tumor microbiome modulation through novel therapeutics, dietary intervention, and precision-medicine approaches. Full article
(This article belongs to the Special Issue Microbiome-Based Interventions in Cancer Immunotherapy)
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20 pages, 1722 KiB  
Review
The Effect of the Gut Microbiota on Systemic and Anti-Tumor Immunity and Response to Systemic Therapy against Cancer
by Azin Aghamajidi and Saman Maleki Vareki
Cancers 2022, 14(15), 3563; https://doi.org/10.3390/cancers14153563 - 22 Jul 2022
Cited by 33 | Viewed by 5685
Abstract
Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal microbiota affects cancer patients’ response to immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1) [...] Read more.
Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal microbiota affects cancer patients’ response to immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Microbiota-induced inflammation possibly contributes to tumor growth and cancer development. Microbiota-derived metabolites can also be converted to carcinogenic agents related to genetic mutations and DNA damage in organs such as the colon. However, other attributes of microbiota, such as greater diversity and specific bacterial species and their metabolites, are linked to better clinical outcomes and potentially improved anti-tumor immunity. In addition, the intratumoral microbial composition strongly affects T-cell-mediated cytotoxicity and anti-tumor immune surveillance, adding more complexity to the cancer-microbiome-immune axis. Despite the emerging clinical evidence for the activity of the gut microbiota in immuno-oncology, the fundamental mechanisms of such activity are not well understood. This review provides an overview of underlying mechanisms by which the gut microbiota and its metabolites enhance or suppress anti-tumor immune responses. Understanding such mechanisms allows for better design of microbiome-specific treatment strategies to improve the clinical outcome in cancer patients undergoing systemic therapy. Full article
(This article belongs to the Special Issue Microbiome-Based Interventions in Cancer Immunotherapy)
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