Breast cancer dormancy and immunotherapy

Dr. Masoud H. Manjili is a leading Guest Editor for Seminars in Cancer Biology focused on Cancer Dormancy and Recurrence. This thematic issue, which contains 10 papers from leading investigators in the area of cancer dormancy, was published in January 2022. Dr. Manjili and colleagues contributed a review paper on “multifaceted functions of chronic inflammation in regulating tumor dormancy and relapse” as well as an editorial paper titled “Pattern recognition of tumor dormancy and relapse beyond cell-intrinsic and cell-extrinsic pathways”. These two papers each covers the key points below:

Manjili MH, Khazaie K. Pattern recognition of tumor dormancy and relapse beynd cell-intrinsic and cell-extrinsic pathways. Seminars in Cancer Biol 78: 1-4, 2022 PMID: 34990835. DOI: 10.1016/j.semcancer.2021.12.008

• Tumor dormancy is a network of molecular interactions which cannot be fully understood by a one-dimensional cause-effect reductionistic approach.
• Tumor dormancy is beyond cell-intrinsic Darwinian selection and cell-extrinsic Lamarckian selection.
• Thermodynamics of tumor dormancy and relapse is centered on ATP synthesis.
• Tumor dormancy is the reflection of a molecular pattern which is independent from its components, similar to the liquid state of water (H₂O) which is independent from the gas state of hydrogen and oxygen. Human brain is evolved to understand the nature by discovering patterns rather than getting lost in details (Figure 1) 

Fig. 1. Cellular pattern recognition of organized molecular particles

Manjili SH, Isbell M, Ghochaghi N, Perkinson T, Manjili MH. Multifaceted functions of chronic inflammation in regulating tumor dormancy and relapse. Seminars in Cancer Biol 7: 17-22, 2022 PMID: 33785450. DOI: 10.1016/j.semcancer.2021.03.023

• An inflammatory immune response is a double-edged sword inducing tumor cell apoptosis when it is transient, and inducing carcinogenesis process in normal cells when it becomes chronic. This could explain a higher incidence of oral cancer in individuals with ill-fitting dentures. Therefore, immunotherapeutic strategies should avoid inducing chronic responses.

• Type I anti-inflammatory immune responses could inhibit tumor relapse while type II inflammation-resolving immune responses could awaken dormant cells and result in metastatic recurrences. This duality can explain a higher incidence of metastatic cancer recurrences following severe injuries and subsequent healing process.

About the Investigators: Masoud H. Manjili, DVM, PhD, is Professor of Microbiology & Immunology, Member of the VCU Institute of Molecular Medicine (VIMM) and member of the VCU Massey Cancer Center (MCC), Virginia Commonwealth University, School of Medicine, Richmond, VA. Khashayarsha Khazaie is a Professor of Immunology at Mayo Clinic. Saeed Manjili is an undergraduate student in biomedical engineering, VCU School of Engineering. Madison Isbell is a MS student in the Manjili laboratory. Negar Ghoochaghi is an undergraduate student at VCU School of Dentistry. Tylor Perkinson is a dentist at Virginia Family Dentistry.