About this Research Topic

Background

In recent years the deaths caused by cancer have led to increasing research on the effective strategy to control tumor growth and limit the incidence of cancer in life. Immune functions decline with age, while the incidence of cancer rises. The advent of immune checkpoint blockade (ICB) has not only revolutionized cancer therapy but also spawned great interest in identifying predictive biomarkers since only one-third of patients show treatment response. The immune system is known to play an important role in cancer progression, although the molecular mechanisms regulating tumor immunity and tumor microenvironment (TME) as well as the impact of aging in cancer immunotherapy are not fully understood. Both aging and cancer are characterized by a series of partially overlapping hallmarks. Disabled macroautophagy and cellular senescence are two hallmarks of aging that exert context-dependent oncosuppressive and pro-tumorigenic effects. Impaired immune function has been implicated in the declining health and higher incidence of cancer in the elderly. However, age-related changes to immunity are not completely understood.

Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling of lymphoid organs, leading to changes in the immune function of the elderly, which is closely related to the development of infections, autoimmune diseases, and malignant tumors. The accumulation of senescent cells is a major cause of age-related inflammation and predisposes to a variety of age-related diseases. Senescent T cells that exhibit abnormal phenotypes, including upregulation of cytotoxic T-lymphocyte-associated protein 4 (CTL-4), and programmed death-ligand 1 (PD-L1) are tightly related to malignant tumors. Senescent cells heterogeneously express the immune checkpoint protein PD-L1 and CTL-4. Consistent with this, administration of PD-1 antibody to naturally aging mice or a mouse model with normal livers or induced non-alcoholic steatohepatitis reduces the total number of PD-L1+ populations in an activated CD8+ T cell-dependent manner, ameliorating various aging-related phenotypes. Moreover, Combination therapy with anti-PD-1 and anti-CTL-4 antibodies resulted in a higher percentage of survival of patients with different solid tumors. Despite the remarkable clinical efficacy of immune checkpoint blockade (ICB) in the treatment of some cancers such as skin, lung, and colorectal cancer, the benefits of ICB in some cancers such as liver and breast cancer are very limited. A clinical trial reported that pembrolizumab, an anti-programmed cell death protein 1 (PD-1) monoclonal antibody, had an objective response rate of just 18% in programmed death-ligand 1 (PD-L1)-expressing advanced Triple-negative breast cancer (TNBC). All this suggests that the heterogeneous expression of PD-L1 and CTL-4 has an important role in the accumulation of senescent cells and inflammation associated with aging, and the elimination of PD-L1+ and CTL-4 senescent cells by immune checkpoint blockade may be a promising strategy for anti-aging therapy. This research topic aims to investigate the therapeutic strategies involving the immune response in aging cells and the regulation of cancer initiation and progression.

We welcome submissions in the form of original research, reviews, mini-reviews, clinical trials, and case reports, that cover (but are not limited) to the following topic

•The impact of aging on the regulation of cancer immune response
•Aging and the impact on immune checkpoint blockage
•Aging and cancer biology
•CD8 T Cell Exhaustion During Aging

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Aging, Immunotherapy, cancer biology, immune system

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