The Microbiome-Immune-Cancer Triangle: How Your Body’s Inner Ecosystem Shapes Cancer Risk and Treatment

For decades, cancer research concentrated on understanding genetic alterations, characterizing tumor behavior, and advancing treatment modalities like radiation therapy, chemotherapy and, more recently, immunotherapy. But science is now uncovering a surprising player in cancer development and treatment response: the microbiome, the vast community of microorganisms (bacteria, fungi, viruses) that live inside and on our bodies[1].

The three-way relationship between the microbiome, the immune system, and cancer is often called the microbiome–immune–cancer triangle. It describes how these systems continuously interact with one another, sometimes helping the body fight cancer, and other times unintentionally helping cancer grow[2].

Understanding this triangle is bringing new hope to patients by opening doors to improved treatment responses and new therapeutic strategies.

A Critical but overlooked player: The Lung Microbiome

An important but often underappreciated part of the microbiome–immune–cancer triangle is the lung microbiome. Whereas healthy lungs were long thought to be sterile organs (free from the presence of viable microorganisms), new molecular methods have uncovered that lungs host their own distinct and complex microbiome community. These microorganisms play an essential role in shaping local immune activity and inflammation.

When this delicate ecosystem becomes unbalanced, it has been linked to chronic lung diseases and even the development and progression of lung cancer. Similar to the gut, microbes in the airways influence immune surveillance and the tumor microenvironment through pattern-recognition signaling, metabolic activity, and cytokine modulation. Emerging evidence suggests that modifying the lung microbiome may support lung cancer prevention and potentially improve responses to immunotherapy, particularly for diseases like non-small cell lung cancer.

Understanding this unique microbial niche widens the scope of microbiome-based cancer strategies, showing that precision oncology must consider not only gut health but lung-specific ecosystems as well[3].

The Microbiome Shapes Immunity

The immune system does not work alone. It relies heavily on support from the microbiome. Research shows that microbial communities influence how immune cells develop, mature, and respond to threats. When the microbiome is healthy and balanced, it supports strong immune surveillance, the body’s ability to detect and destroy abnormal cells before they become harmful. However, when the microbiome becomes disturbed (a state called dysbiosis), immune regulation weakens. This imbalance can trigger chronic inflammation, reduce the power of protective immune cells, and create an environment that allows tumors to grow more easily[1].

Put simply, your microbial community helps train your immune system every day — and its balance matters.

How the Microbiome Influences Cancer Risk

Scientists are increasingly discovering that certain microbes can protect against cancer, while others may promote tumor formation. Dysbiosis can shift the immune system into an inflammatory state that supports tumor development and progression.

Chronic inflammation can damage DNA, fuel rapid cell growth, and weaken immune cells that would normally keep cancer cells in check.

Some microbes produce helpful metabolites like short-chain fatty acids that reduce inflammation. Others may produce toxins that damage cells or interfere with the immune response. This means cancer risk is partly shaped by the microscopic world living inside us[4]. In lung cancer, shifts in the biomass, distribution, and composition of the lung microbiome have been associated with tumor initiation and progression, suggesting that local microbial communities can directly shape carcinogenic risk in the airways. Disturbances along the gut–lung axis further illustrate how dysbiosis in the gut may reverberate to the lungs, altering systemic and mucosal immunity in ways that can promote or restrain lung tumor development.

The Microbiome Shapes Response to Cancer Treatment

One of the most significant insights from recent scientific research is that the microbiome strongly affects how well patients respond to immunotherapy.

Microbiome influences both innate and adaptive immunity, altering how T cells and other key immune cells behave during cancer therapy.

Studies show that patients with a diverse, balanced gut microbiome respond better to immune checkpoint inhibitors, a class of immunotherapy drugs. Certain bacterial species can enhance T-cell activation, boost antigen presentation, and improve the overall anti-tumor response.

On the other hand, dysbiosis is linked to poorer response rates, treatment resistance, and more severe side effects in some patients.

This finding is so compelling that researchers are exploring whether modifying the microbiome could improve cancer treatment outcomes with immunotherapy[5].

Immune Cells, Microbes, and Tumors: A Three-Way Conversation

The triangle concept illustrates that cancer is not just a disease of malignant cells, but a disease of ecosystems. Immune cells, microbes, and tumor cells constantly interact through chemical signals, inflammatory mediators, and metabolic products.

Rather than a single fixed state, a “healthy” microbiome in cancer care is best thought of as a diverse, resilient community with a beneficial composition of microbes and metabolites that supports balanced immune responses. In NSCLC and other cancers, specific patterns of microbial diversity and composition, rather than the mere presence of bacteria, have been linked to stronger and more durable responses to immunotherapy.

Some microbes can even affect how tumors behave by altering the acidity of tissues, modifying metabolic pathways, or influencing immune checkpoints.

This interconnected network goes some way to explain why cancer can behave so differently from person to person[4, 5].

Can We Use the Microbiome to Fight Cancer?

This question is now at the center of cutting-edge research. Scientists are exploring several exciting strategies:

1. Microbiome-based biomarkers
Certain microbial patterns can predict how well a patient might respond to therapy. For example, specific gut bacteria have been associated with better immunotherapy outcomes[6]. In NSCLC, for example, patterns in the lung tissue microbiome can help distinguish adenocarcinoma from squamous cell carcinoma, highlighting how microbial signatures within the tumor microenvironment may serve as non‑traditional biomarkers for diagnosis and precision treatment planning.

2. Probiotics and diet-based modulation
Researchers are investigating whether foods, probiotics, or prebiotics can strengthen the microbiome enough to improve immune function[4].

3. Fecal microbiota transplantation (FMT)
Some clinical trials are assessing whether transferring microbiome material from a patient who responds well to immunotherapy can boost the response in a patient who does not[7].

4. Targeted microbial therapies
Future treatments may involve engineered bacteria that deliver drugs, modulate immune cells, or change local tissue environments.

We are entering a new era in cancer care where treatment may not only target the tumor, but also the ecosystem surrounding it.

The Future of Cancer Care Through the Microbiome Lens

As research expands, the microbiome–immune–cancer triangle is becoming a powerful framework for understanding why cancers behave the way they do and how treatments can be improved. It shines a light on the importance of whole-body health and the role that unseen microscopic partners play in shaping immunity. It also offers hope that by restoring balance to the microbiome, we may boost the effectiveness of modern therapies and improve long-term outcomes.

This growing body of research highlights one core principle: cancer cannot be understood in isolation, and at Helix BioPharma, we remain closely attuned to the scientific advances that reinforce this view. Microbial metabolites and immune-modulating signals influence systemic inflammation, cytokine profiles and immune cell activation. These systemic effects can ultimately alter how immune cells behave once they enter the tumor microenvironment (TME), affecting everything from immune surveillance to treatment responsiveness. In other words, the microbiome acts upstream, shaping the body’s immune tone and metabolic state, whereas the TME represents the downstream arena where these influences play out. The more we understand these upstream and downstream influences, the closer we move to pushing the boundaries of what cancer treatment can achieve.

References:

1. Donald K, Finlay BB. Mechanisms of microbe-mediated immune development in the context of antibiotics and asthma. Front Allergy. 2024 Oct 14;5:1469426. doi: 10.3389/falgy.2024.1469426. PMID: 39469482; PMCID: PMC11513386.

2. Zhang J, Dai Z, Yan C, Zhang W, Wang D, Tang D. A new biological triangle in cancer: intestinal microbiota, immune checkpoint inhibitors and antibiotics. Clin Transl Oncol. 2021 Dec;23(12):2415-2430. doi: 10.1007/s12094-021-02659-w. Epub 2021 Jun 14. PMID: 34125407; PMCID: PMC8557192.

3. Bou Zerdan M, Kassab J, Meouchy P, Haroun E, Nehme R, Bou Zerdan M, Fahed G, Petrosino M, Dutta D, Graziano S. The Lung Microbiota and Lung Cancer: A Growing Relationship. Cancers (Basel). 2022 Oct 1;14(19):4813. doi: 10.3390/cancers14194813. PMID: 36230736; PMCID: PMC9563611.

4. Eiman L, Moazzam K, Anjum S, Kausar H, Sharif EAM, Ibrahim WN. Gut dysbiosis in cancer immunotherapy: microbiota-mediated resistance and emerging treatments. Front Immunol. 2025 Aug 25;16:1575452. doi: 10.3389/fimmu.2025.1575452. PMID: 40927726; PMCID: PMC12415008.

5. Li X, Zhang S, Guo G, Han J, Yu J. Gut microbiome in modulating immune checkpoint inhibitors. EBioMedicine. 2022 Aug;82:104163. doi: 10.1016/j.ebiom.2022.104163. Epub 2022 Jul 15. PMID: 35841869; PMCID: PMC9297075.

6. Zhou Y, Han W, Feng Y, Wang Y, Liu X, Sun T, Xu J. Revealing gut microbiota biomarkers associated with melanoma immunotherapy response and key bacteria-fungi interaction relationships: evidence from metagenomics, machine learning, and SHAP methodology. Front Immunol. 2025 Mar 18;16:1539653. doi: 10.3389/fimmu.2025.1539653. PMID: 40170844; PMCID: PMC11959079.

7. Lin A, Huang L, Jiang A, Zhu L, Mou W, Li Y, Zhang C, Liu Z, Zhang J, Cheng Q, Wei T, Luo P. Microbiota boost immunotherapy? A meta-analysis dives into fecal microbiota transplantation and immune checkpoint inhibitors. BMC Med. 2025 Jun 9;23(1):341. doi: 10.1186/s12916-025-04183-y. PMID: 40484955; PMCID: PMC12147380.

Jacek Antas

Chief Executive Officer

Jacek Antas is a shareholder of the Company, has spent more than 25 years in the financial services industry holding various positions in sales and consulting.

Mr. Antas obtained a master’s degree from the Warsaw School of Economics and has served as a board member of various
companies throughout his career.

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James B. Murphy

Chief Financial Officer

Mr. Murphy is a certified public accountant with over thirty years of experience in finance and operations management. He is currently a consultant with Danforth Advisors LLC (“Danforth”), a leading provider of outsourced strategic and operational specialists across functions in the life sciences industry. While at Danforth, Mr. Murphy has served over fifteen private and publicly held life sciences companies as CFO and CFO Advisor, helping them secure over USD 0.5 billion in financing and successfully execute pivotal asset transactions. Mr. Murphy functions as a consultant to Helix pursuant to a consulting agreement between the Company and Danforth.

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Thomas Mehrling

Medical Adviser

Thomas Mehrling (PhD in Pharmacology and MD) has over 20 years’ experience in multinational Pharma companies developing novel oncology compounds from preclinical research through to registration. Prior to entering the industry, he spent 13 years as an MD at the University Hospital in Frankfurt, working on preclinical and translational projects. He served as Director of European Oncology at Mundipharma International (2003–2013), building the company’s first European oncology business from the ground up out of Cambridge, UK, and completing the clinical development, registration and launch of two major products in Europe, DepoCyte® and Levact® (Ribomustin® and Treanda®). In 2013, he led the establishment of the Mundipharma Group’s start-up, Mundipharma EDO, developing anti-cancer therapeutics for solid tumours out of Basel, Switzerland.

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Kim Gaspar

Director Quality Assurance

Kim is the Director of Quality Assurance at Helix BioPharma Corp. An experienced quality assurance professional with expertise in Canadian, US, and EU regulations, she has been involved in all aspects of Phase I/II biopharmaceutical product development over the years, including regulatory submissions, QC laboratory compliance, tech transfer and third-party oversight of CMC activities, clinical QA, and bioanalytical data analysis. Kim joined Helix in 2000, transitioning into QA in 2003. She holds a B.Sc in Biochemistry and a Ph.D in Veterinary Physiological Sciences, both from the University of Saskatchewan.

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Brenda Lee

Director Clinical Operations

Brenda is the Clinical Operations Director at Helix Biopharma Corp. A clinical research operations professional with 25 years of experience managing clinical trials, ranging from early Phase I to late Phase IIIb/IV studies, she brings experience in clinical study protocol writing and development, trial start-up and vendor management, and a proven track record in planning and managing clinical trials to quality standards, timelines and budget. Brenda joined Helix Biopharma Corp. in 2018, working to advance the clinical program of L-DOS47. She holds B.Sc and M.Sc. degrees from the University of Toronto, specializing in Nutritional Sciences and Human Biology.

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Jerzy Leszczynski

Director

Jerzy Leszczynski is a shareholder of the Company, has spent more than 35 years developing businesses and has served in the capacity of board member of various real estate development companies. Mr. Leszczynski obtained his Master of Science in Chemistry from the Warsaw Institute of Technology.

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Janusz Grabski

Director, Chair of Audit Committee

Janusz (John) Grabski is a lawyer specialized in corporate and real estate law with over twenty years of experience.

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Malgorzata Laube

Director

Malgorzata Laube has over 19 years of experience in nuclear medicine. In her last role with Alberta Health Services, she was the Department Supervisor, Nuclear Medicine at Royal Alexandra Hospital. Ms. Laube obtained a MSc degree in Environmental Engineering from the Warsaw University of Technology and is based in Edmonton, Alberta, Canada.

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Jacek Antas

Chairman of the Board

Jacek Antas is a shareholder of the Company, has spent more than 25 years in the financial services industry holding various positions in sales and consulting.

Mr. Antas obtained a master’s degree from the Warsaw School of Economics and has served as a board member of various
companies throughout his career.

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Jonathan Davis

Advisor, ADC Discovery

Jonathan Davis received his Ph.D. from University of California, San Francisco, where he studied protein structure and function using NMR. After a post-doc at Harvard Medical School exploring RNA selection and structure in the labs of Jack Szostak and Gerhard Wagner, he went to work at EMD Serono, where his work involved improving antibody-based therapeutics, inventing a platform technology for generating heterodimeric Fcs as a basis for multifunctional molecules, and developing a novel scaffold based on an artificially-designed protein from David Baker’s lab. In 2008 he took a job at Bristol-Myers Squibb in Waltham/Cambridge MA, working on antibody discovery and platform development in a wide range of therapeutic areas, with a particular focus on multispecific therapeutics. He moved to Madison, WI in 2019 to take on the role of VP of Innovation and Strategy at Invenra, a biotech focused on bispecific antibodies, and where he is currently head of the Scientific Advisory Board. In early 2024 he left the corporate world to found Creative Antibodies, a consulting firm that helps guide companies to successful antibody discovery and development projects, from mAbs to multispecifics, ADCs, and other formats. Outside of science, Jonathan is a conservatory trained cellist, plays numerous other instruments, and founded the UCSF Orchestra (now Symphony Parnassus) in San Francisco, where he was Music Director for six years.

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Davide Guggi

Advisor, CMC

Davide graduated as a pharmacist and received his PhD in Pharmaceutical Technology and Biotechnology from the University of Vienna. He has over 20 years of experience in the pharmaceutical industry, principally in the field of oncology. At the beginning of his career, Davide led oncology business units and commercial departments at Mundipharma and Gilead across Austria and Eastern Europe. Since over 10 years he has been working as a CMC expert, covering operational and regulatory CMC functions on behalf of over 20 different small- and medium-sized biotech companies across the world. He has served as CMC Director and CSO/CTO for several years, developing both small molecules and biologics (mABs, Fab, ADCs and Radio-immuno-conjugates) from early discovery to NDA/BLA in the US, EU and Canada, with a focus on First-in-Human and Phase I/II studies in oncology indications.

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Tumor Defense Breaker™, L-DOS47

L‑DOS47 is a first‑in‑class, clinical-stage antibody‑enzyme conjugate designed to deliver a game-changing assist to anti-cancer immunity and today’s leading cancer immunotherapies for the treatment of prevalent, hard-to-treat solid tumors. The compound precisely targets CEACAM6, a cell-surface protein overexpressed in non‑small cell lung cancer (NSCLC) and other aggressive tumors, where it delivers an enzymatic payload that raises the extracellular pH of the acidic tumor microenvironment (TME). By neutralizing tumor acidity, L-DOS47 restores immune cell infiltration and activity, helps turn immunologically “cold” tumors “hot”, and enhances the therapeutic reach of immune checkpoint inhibitors. With patented composition-of-matter coverage through 2036 and demonstrated synergy with PD-1 inhibitor, pembrolizumab, L-DOS47 is poised to significantly increase the efficacy of immune checkpoint blockade and unlock broader and more durable responses in NSCLC and other aggressive solid tumors.



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