Immunosenescence: a key player in cancer development

Abstract

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. T cell–output decline is an important feature of immunosenescence as well as the production of senescence-associated secretory phenotype, increased glycolysis, and reactive oxygen species. Senescent T cells exhibit abnormal phenotypes, including downregulation of CD27, CD28, and upregulation of CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, and cytotoxic T-lymphocyte-associated protein 4, which are tightly related to malignant tumors. The role of immunosenescence in tumors is sophisticated: the many factors involved include cAMP, glucose competition, and oncogenic stress in the tumor microenvironment, which can induce the senescence of T cells, macrophages, natural killer cells, and dendritic cells. Accordingly, these senescent immune cells could also affect tumor progression. In addition, the effect of immunosenescence on the response to immune checkpoint blocking antibody therapy so far is ambiguous due to the low participation of elderly cancer patients in clinical trials. Furthermore, many other senescence-related interventions could be possible with genetic and pharmacological methods, including mTOR inhibition, interleukin-7 recombination, and NAD+ activation. Overall, this review aims to highlight the characteristics of immunosenescence and its impact on malignant tumors and immunotherapy, especially the future directions of tumor treatment through senescence-focused strategies.

Brafmutation induces rapid neoplastic transformation in the aged and aberrantly methylated intestinal epithelium

“…Alternatively, the microenvironment of the aged intestine may be comprised of different immune cells, leading to the altered gene expression signal that we observed. Immunosensence is associated with cancer, 42 and identifying whether this may be contributing to the elevated risk of neoplasia in the context of Braf mutation remains an important area for future studies.…”

Polyfunctional KLRG-1+CD57+ Senescent CD4+ T Cells Infiltrate Tumors and Are Expanded in Peripheral Blood From Breast Cancer Patients

“…T cell senescence was initially described as a natural process occurring during aging (1). Later, it was described that senescent CD8 + T cells were increased in young individuals with chronic infections, autoimmune diseases, and cancer (2)(3)(4)(5). Few reports have focused on senescent CD4 + T cells, possibly due to the lower susceptibility of this cell population to become senescent in comparison to CD8 + T lymphocytes (6).…”

Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly

“…Likewise, the immunosenescence and inflammaging could thus be part of the lethality amongst the elderly with COVID-19 [ 14 ]. Furthermore, increases in autoimmunity and cancer seems also be related to an aging immune system [ 15 , 16 ] and the facilitation of various internal, orthopedic, psychological and neurodegenerative conditions has been intensively discussed [ 17 , 18 ].…”