Immunotherapy of Cancer: Targeting Cancer During Active Disease or During Dormancy?

Shah, Sujay; Zarei, Melika; Manjili, Saeed H.; Guruli, Georgi; Wang, Xiangyang; Manjili, Masoud H.

doi:10.2217/imt-2017-0044

Cited by 7 publications

(4 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tumor-host interactions are progressively known as crucial constituents of cancer growth or inhibition. Particularly, infiltrating immune cells are critical features of the tumor microenvironment [103]. Cancer cells are encircled by stromal cells, including macrophages, fibroblasts, mast cells, neutrophils, and lymphocytes, which communicate through an intricate system of intercellular signaling pathways, mediated by cytokines, adhesion molecules, and the receptor-ligand network [42].…”

Section: Cancer Immune-mediated Dormancymentioning

confidence: 99%

Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

Jahanban‐Esfahlan

Seidi

Manjili

et al. 2019

Cancers

View full text Add to dashboard Cite

Tumor dormancy, a clinically undetectable state of cancer, makes a major contribution to the development of multidrug resistance (MDR), minimum residual disease (MRD), tumor outgrowth, cancer relapse, and metastasis. Despite its high incidence, the whole picture of dormancy-regulated molecular programs is far from clear. That is, it is unknown when and which dormant cells will resume proliferation causing late relapse, and which will remain asymptomatic and harmless to their hosts. Thus, identification of dormancy-related culprits and understanding their roles can help predict cancer prognosis and may increase the probability of timely therapeutic intervention for the desired outcome. Here, we provide a comprehensive review of the dormancy-dictated molecular mechanisms, including angiogenic switch, immune escape, cancer stem cells, extracellular matrix (ECM) remodeling, metabolic reprogramming, miRNAs, epigenetic modifications, and stress-induced p38 signaling pathways. Further, we analyze the possibility of leveraging these dormancy-related molecular cues to outmaneuver cancer and discuss the implications of such approaches in cancer treatment.

show abstract

Section: Cancer Immune-mediated Dormancymentioning

confidence: 99%

Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

Jahanban‐Esfahlan

Seidi

Manjili

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…Immune therapy for dormant micrometastases has been proposed based on preclinical and clinical evidence [371]. Randomized phase II clinical trials of patients with nodepositive or high-risk node-negative Her2 + BC after definitive therapy and no clinical evidence of disease demonstrated a potential clinical benefit in survival [372,373].…”

Section: Potential Therapeutic Approachesmentioning

confidence: 99%

“…Cancer cells that are truly dormant after chemotherapy and negative for Ki67 are susceptible to immune modulation, whereas cells that are low for Ki67 are not [374]. Based on these observations, it has been proposed that immunotherapy should be administered after therapeutic conditioning to suppress tumor immunoediting that permits escape from immunotherapy or in combination with targeted therapies [371].…”

Section: Potential Therapeutic Approachesmentioning

confidence: 99%

Awakening of Dormant Breast Cancer Cells in the Bone Marrow

Wieder

2023

Cancers

View full text Add to dashboard Cite

Up to 40% of patients with breast cancer (BC) have metastatic cells in the bone marrow (BM) at the initial diagnosis of localized disease. Despite definitive systemic adjuvant therapy, these cells survive in the BM microenvironment, enter a dormant state and recur stochastically for more than 20 years. Once they begin to proliferate, recurrent macrometastases are not curable, and patients generally succumb to their disease. Many potential mechanisms for initiating recurrence have been proposed, but no definitive predictive data have been generated. This manuscript reviews the proposed mechanisms that maintain BC cell dormancy in the BM microenvironment and discusses the data supporting specific mechanisms for recurrence. It addresses the well-described mechanisms of secretory senescence, inflammation, aging, adipogenic BM conversion, autophagy, systemic effects of trauma and surgery, sympathetic signaling, transient angiogenic bursts, hypercoagulable states, osteoclast activation, and epigenetic modifications of dormant cells. This review addresses proposed approaches for either eliminating micrometastases or maintaining a dormant state.

show abstract

“…Therefore, immunotherapy is the only option for the treatment of tumor dormancy. In fact, we have demonstrated that dormant tumor cells remain highly susceptible to immunotherapy if targeted before clinical recurrence ( 63 ).…”

Section: Immunotherapeutic Targeting Of Tumor Dormancy For the Prevenmentioning

confidence: 99%

The premise of personalized immunotherapy for cancer dormancy

Manjili¹

2020

Oncogene

View full text Add to dashboard Cite

Progress in cancer therapies has resulted in improved survival of patients with early stage breast cancer. However, mortality remains high in patients with distant recurrence of the disease after initially successful treatment of early stage breast cancer. To this end, tumor recurrences have been attributed to the presence of dormant tumor cells in breast cancer patients and cancer survivors. Current clinical practice guidelines recommend a “wait and watch” approach for tumor recurrence. This is because of our limited understanding of tumor dormancy. Dormant tumor cells are quiescent, and thus, do not respond to chemotherapies or radiation therapies, and they are not operable. Therefore, immunotherapy is the only option for the treatment of tumor dormancy. However, gaps in our knowledge as to dormancy-specific antigens prevent a relapse preventing vaccine design. Here, we provide a critical review of cancer immunotherapy, and discuss empirical evidence related to naturally-occurring tumor dormancy and treatment-induced tumor dormancy at the site of primary tumor and in distant organs before and after cancer therapies. Finally, we suggest that personalized vaccines targeting dormancy-associated neoantigens, which can be given to patients with early stage disease after the completion of neoadjuvant therapies and tumor resection as well as to cancer survivors could eliminate relapse causing dormant cells and offer a cure for cancer.

show abstract

Immunotherapy of Cancer: Targeting Cancer During Active Disease or During Dormancy?

Cited by 7 publications

References 64 publications

Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

Tumor Cell Dormancy: Threat or Opportunity in the Fight against Cancer

Awakening of Dormant Breast Cancer Cells in the Bone Marrow

The premise of personalized immunotherapy for cancer dormancy

Contact Info

Product

Resources

About