Anticancer Immunity: Reviewing the Potential of Probiotics

The human body is colonized by microbial cells that are estimated to be as abundant as human cells, yet their genome is roughly 100 times the human genome, providing significantly more genetic diversity. The past decade has observed an explosion of interest in examining the existence of microbiota in the human body and understanding its role in various diseases, including prostate cancer. Studies show that probiotics provide positive results in prostate cancer prevention and treatment. However, some studies argue that they should not be used, putting forward the fact they may cause infection in patients with very weak immunity. This chapter summarizes key microbiota alterations observed in prostate cancer niches, their association with clinical stages, and their potential use in anticancer therapy and management. In addition, the chapter discusses microbiota-based therapeutic approaches for prostate cancer. 

Bladder cancer accounts for an estimated 500,000 new cases and 200,000 deaths annually. The prevalence of bladder cancer is high, with more than 1.6 million people affected worldwide. Modern techniques not based on microbiological cultures, such as Next Generation Sequencing (NGS) of the 16S rRNA gene, have provided robust evidence that a urinary commensal microbiota exists. Few studies have shown a detailed analysis of the urinary microbiota in patients with bladder cancer. Therefore, the nature and role of many relevant bladder bacteria in the initiation and progress of bladder cancer remain under investigation. This chapter describes the main studies in this regard, as well as the underlying mechanisms, mainly immune-based. Moreover, if we talk about bladder cancer and the feasibility of probiotics as an alternative treatment acting on the microbiota, we must start by mentioning the functionality of the Bacille Calmette-Guérin (BCG) vaccine. Based on the immunogenic performance of the BCG vaccine, new therapies with probiotic bacteria were proposed, and in vivo and in vitro studies were performed with positive results in terms of tumor size reduction and recurrence reduction. Finally, the potential use of Bifidobacterium as a vector in specific gene therapy against bladder cancer is described. 

Pancreatic cancer is still one of the malignancies with a very poor prognosis worldwide. In the recent past, the gut microbiota has been shown to have a role in pancreatic cancer patients’ survival and response to the therapy. Out of the possible mechanisms, the role of gut microbiota in shaping the microbial composition of pancreatic tumor and its effect on intra-tumor immune modulation has emerged as a potential therapeutic strategy. Modulation of gut microbiota for targeting pancreatic cancer initiation, progression and therapy could be achieved through different processes like treatment through faecal microbiota transplantation (FMT), antibiotics, prebiotics, probiotics, and synbiotics. In the recent past, various clinical and experimental pieces of evidence have demonstrated the efficacy of probiotics in cancer prevention, treatment and management. In this chapter, efforts have been directed towards summarizing the prospects and challenges associated with the use of probiotics and probiotics-derived products against pancreatic cancer. 

Oral and Oropharyngeal cancer constitute severe community health problems across the globe. Annually about 400,000 new cases of oral cancer are detected globally. Oral cancer is the sixth most common type of cancer in the world, and it is the leading cause of death, particularly in the Southeast Asian region. In recent times, a gradual surge in cases of oral cancer has been witnessed in many developed countries, such as France. In the search for safe and effective therapy for cancer, probiotics have gained recent attention from many research groups worldwide. Probiotics have an advantageous effect on human health, which are experimentally and clinically proven to exert overall beneficial effects. Probiotics are generally defined as the sum of harmless live bacteria, molds, and yeasts that have beneficial effects on human health. This chapter discusses the potential role of probiotics as anticancer adjuvants owing to their modulatory effect on anticancer immunity. Anticancer immunity-based properties include the restraint of the growth of microbiota engaged in the making of mutagens and carcinogens and change in the metabolism of carcinogen and DNA resistance from oxidative damage as well as regulation of the immune system. At present, chemotherapy and immunotherapy are mostly preferred for the treatment of oral cancer, but these treatments have the foremost disadvantage that causes drug resistance and recurrence of the disease. To overcome such problems, nowadays, probiotics have been recommended as complementary treatment modalities for the development of new therapy along with standard chemotherapeutic and immunotherapeutic agents by improving the immune system. Specific microbiota in the human body supplies the production of the most useful metabolites that exert optimistic properties on the immune system in opposition to various diseases such as cancer.

Cancer is one of the major diseases that seriously endanger human health worldwide. The risk of developing cancer depends on genetic factors and the body's immune system. The intestinal microbiome plays an essential role in maintaining homeostasis in the human body. After cardiovascular disease, the second-largest illness in terms of morbidity and mortality rate is cancer. Cancer has always been the focus of human attention worldwide, which makes it a research hotspot in the medical field. In recent years, the consumption of probiotics has been fetching in health-promoting foods for humans, therapeutic, prophylactic and growth supplements for animal production and human health. In medicine, various studies have demonstrated that probiotics can help in improving the immune system and intestinal health and the effect of probiotic therapy on antitumor treatment-related side effects; combined use of probiotic strains did have a positive protective effect for patients with specific immune function. Healthy gut microbiota has positive impacts not just on immune system activity but also on thyroid function. Dysbiosis has been detected in autoimmune thyroid diseases (AITD) and thyroid cancer, where many carcinogenic and inflammatory bacterial strains were found. The nature of the gut microbiome also influences the availability of important micronutrients for the thyroid gland. Iodine, iron, and copper are required for thyroid hormone synthesis, selenium and zinc are required for T4 to T3 conversion, and vitamin D aids in immune response regulation. These micronutrients are frequently lacking in AITDs, and lead to thyroid dysfunction. Thyroid-stimulating hormone (TSH) and T3 levels may fluctuate due to bariatric surgery, resulting in insufficient absorption of essential nutrients. Probiotic supplementation positively affected thyroid hormones and thyroid function in general. This chapter summarizes the role, mechanism of probiotics, clinical trials and effects of probiotics in thyroid cancer.

The gut microbiome can play an important role in maintaining homeostasis in the human body. An imbalance in the gut microbiome can lead to pro-inflammatory immune responses and the initiation of disease processes, including cancer. Lymphocytes play a significant role in the reaction to bacterial colonization, mainly by prompting a safe reaction to initiation. Most immunologically inhabitant cells are continually signaled by dendritic cells or other antigen-presenting cells that collect intestinal samples. Therefore, the microbiota is a pivotal contributor to developing lymphoma, and specific changes to microbiota composition could help prevent the risk. Microbial morphology can affect and control humanoids. The difference in the composition of these microbes is associated with tumor development. Moreover, with the increased exploration and knowledge of the connection between human microbiota and carcinogenesis, the use of these findings to predict, prevent, or diagnose lymphomas has attracted great attention. Probiotics have gained increasing medical significance due to their beneficial effect on the human body, which has been linked to the prevention and support of the treatment of many chronic diseases, including cancer, in the absence of side effects. Chemotherapy and immunotherapy are extensively used for the treatment of lymphomas. But these treatments have various side effects. There is much evidence that probiotics can help in preventing cancer and support anticancer therapy. This chapter presents the latest advances in research into the effectiveness of probiotics in the prevention and treatment support of lymphoma. In addition, the chapter also describes the potential mechanisms of probiotic chemoprevention and the advisability of using probiotics in the prevention of lymphoma. 

The gut microbiota is composed of commensal bacteria and other microorganisms residing in the gastrointestinal tract. The gut microbiome plays a significant role in orchestrating human homeostasis via modulation of key steps involving metabolism, inflammation and probably the most important of all, immunity. As far as renal carcinoma is concerned, the diversity of the gut microbiome is a vital risk factor in the onset and progression of renal cancer. Since probiotics have the potential to positively amend the composition of gut microbiota, they have gained increasing medical significance. The development of targeted immunotherapies has changed the scenario of clinical management of renal carcinoma, but their use has been hampered by increased host refractoriness and adverse effects. Recent studies show that gut microbiota is involved in modulating the response to immunotherapy and the host's susceptibility to dose-limiting adverse effects. Hence, manipulation of the gut microbiome by probiotics is fast emerging as a feasible mechanism to improve responsiveness to immunotherapy. In this chapter, we discuss the available evidence of the potential role of modulation of microbiota by probiotics in the management of renal carcinoma.

Cancer is a multifactorial disease and is the second leading cause of death globally. The strength of the immune system is critical to fighting against cancer. It has been documented that probiotics play a crucial role in successfully preventing and treating several forms of cancer through microbiota and immunological modulation. Probiotics-related research has gained attention due to its ability to modulate cancer via different pathways like downregulation of oncogene expression, inhibition of kinases, induction of autophagy, reactivation of tumor suppressors, etc. Probiotics are used as an adjuvant in anticancer therapy because of their unique properties. It helps the human immune system function at its best to detect and kill the cells that can become cancerous. Administering a healthy or immune-potentiating probiotic as an immunotherapy adjuvant is a more practical way to deal with several diseases in clinical settings. Apart from direct anticancer effects, microbiome-derived products, especially metabolites, directly affect cancer cells and indirectly act as signals for immunomodulatory action. Probiotics can efficiently produce or release compounds/metabolites with anticarcinogenic activity. Some studies have shown that combining anticancer drugs with probiotics can reduce the harmful effects of chemotherapy while also improving the therapeutic impact. Despite all these concepts and proofs, the regulation of microbial intake as a medication category poses a therapeutic challenge, and the data are still limited. The viability of probiotics as adjuvants offering advantages by targeting cancer and reducing anticancer side effects, particularly in cancer patients, needs to be investigated further.

 Cancer remains a daunting task for clinicians and scientists. Many scientists across the globe are toiling in their labs to find an effective and safe treatment modality for cancer. Although significant stride has been achieved in the field of cancer treatment, and millions of precious lives have been saved using available therapeutic strategies, viz. chemotherapy, radiation therapy, biologics and surgical intervention. However, the search for the panacea for cancer is still not over, and new dimensions are being constantly explored. Maneuvering the immune system for controlling and treating cancer is a new fascinating field, and rigorous researches are underway. The importance of anticancer immunity as a promising treatment approach has been recognised even by the Nobel Prize Authority and James P. Allison and Tasuku Honjo were jointly awarded the 2018 Nobel Prize in Physiology or Medicine for their revolutionary research in cancer immunotherapy. This chapter discusses the different aspects of immune system response vis a vis cancer development and strategies to manipulate the immune system through prebiotics and postbiotics to control and cure the different types of cancer. Prebiotics and postbiotics are being explored extensively for their role in modifying disease progression and control of cancer. Prebiotics and postbiotics are considered safe alternatives to manipulate the immune system in order to get therapeutic benefits for cancer. 

Probiotics are defined as “viable microorganisms which, when administered in adequate amounts, promote health benefits on the host”. These health benefits may include maintaining a healthy gut microbiota, reducing cholesterol levels, formation of antimicrobial agents and vitamins, competitive inhibition of pathogenic bacteria in terms of attachment site and nutrition, immunity-boosting, improvement of calcium absorption, preventing constipation, and increased trans-epithelial resistance. Cancer is expressed as the abnormal division and reproduction of cells and has a multifactorial pathology. In mortality, cancer is in second place worldwide, which is evident from the report that one out of every four deaths in the USA is due to cancer. Furthermore, the prevalence of cancer is 24% and 21% for men and women, respectively. Probiotics used in the prevention and treatment of cancer often prevent early death due to complications caused by infection, particularly in GIT. The current article mainly discusses different conventional and non-conventional formulations of probiotics. It also discusses probiotics and immunity against cancer, safety, and current regulation regarding probiotics. 

Anticancer immunotherapy is a promising approach to the treatment of cancer. Probiotics have been introduced as a potential candidate to contribute to the success of the anticancer immunotherapy approach. However, current and future challenges in probiotics-based anticancer immunotherapy should be addressed to allow better utilization and understanding of the limitations of the use of probiotics in such an approach. This chapter highlights the safety issues related to probiotics use in human subjects, such as adverse effects, bacteremia and risk-benefits analysis. It also briefly discusses the status of the use of probiotics in human clinical trials to assess the therapeutic effects of probiotics in the anticancer immunotherapy approach. More human clinical trials are needed and should follow the principles of Good Clinical Practice (GCP), with methodologies and end-points, useful to define outcomes by considering their physiological and clinical meaning. Challenges related to the properties of different probiotic species, their viability, and their strain-specific therapeutic effects have been highlighted. It also spotlights the contemporary state of personalized treatment for cancer patients using selected probiotic strains individually and/or in combination. Careful consideration should be given to these issues in the use of probiotic supplements in anticancer immunotherapy in clinical practice in the future.