Vol.:(0123456789) 1 3 Journal of Cancer Research and Clinical Oncology https://doi.org/10.1007/s00432-020-03424-2 REVIEW – CANCER RESEARCH The role of plant‑derived natural substances as immunomodulatory agents in carcinogenesis Marek Samec 1  · Alena Liskova 1  · Lenka Koklesova 1  · Samson Mathews Samuel 2  · Radovan Murin 3  · Pavol Zubor 4  · Jan Bujnak 5  · Taeg Kyu Kwon 6  · Dietrich Büsselberg 2  · Robert Prosecky 7  · Martin Caprnda 8  · Luis Rodrigo 9  · Rachele Ciccocioppo 10  · Peter Kruzliak 11  · Peter Kubatka 12 Received: 28 September 2020 / Accepted: 8 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract The role of immune system in carcinogenesis represents fundamental events associated with cancer eradication; however, tumor evolution is connected with various mechanisms of tumor evasion and progression of cancer. Based on recent evidence, phytochemicals are directly associated with immunomodulation of the innate and adaptive immunity via diferent mechanisms of action including stimulation and amplifcation of immune cells, humoral compartments, and associated molecules. This comprehensive study focuses on immunomodulating potential of phytochemicals (mixture in plants or separately such as individual phytochemical) and their impact on regulation of immune response during cancer development, immune tolerance, and immune escape. Clinical application of phytochemicals as modulators of host immunity against cancer may represent perspective approach in anticancer therapy. Keywords Cancer · Immunomodulation · Cytokines · Phytochemicals · Preclinical and clinical research * Peter Kruzliak kruzliakpeter@gmail.com * Peter Kubatka peter.kubatka@uniba.sk 1 Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia 2 Department of Physiology and Biophysics, Weill Cornell Medicine‑Qatar, Education City, Qatar Foundation, Doha, Qatar 3 Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia 4 Department of Gynecologic Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway 5 Department of Obstetrics and Gynaecology, Kukuras Michalovce Hospital, Michalovce, Slovakia 6 Department of Immunology and School of Medicine, Keimyung University, Dalseo‑Gu, Daegu, Korea 7 2nd Department of Internal Medicine, Faculty of Medicine, Masaryk University and St. Anne’s University Hospital, Brno, Czech Republic 8 1st Department of Internal Medicine, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia 9 Faculty of Medicine, University of Oviedo, Central University Hospital of Asturias (HUCA), Oviedo, Spain 10 Gastroenterology Unit, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Policlinico GB Rossi, University of Verona, Verona, Italy 11 2nd Department of Surgery, Faculty of Medicine, Masaryk University and St. Anne’s University Hospital, Pekarska 53, 656 91 Brno, Czech Republic 12 Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia