Abstract
In our previous study, we found that low thymic output and short telomere length were associated with a higher risk of tumor in elderly cancer patients. Here, we aimed to examine in depth the impact of immunological and biological senescence and immune activation on disease outcome in elderly patients with colorectal cancer (CRC).Peripheral blood samples from 81 CRC patients were studied for immune activation, immune senescence and recent thymic emigrant(RTE) CD4 and CD8 cells by flow cytometry. T-cell receptor rearrangement excision circle (TREC) levels and telomere lengths were measured by real-time PCR. Plasma levels of microbial translocation markers, LPS and sCD14, were quantified by ELISA. While TREC levels and telomere length were not prognostic of disease outcome, high percentages of immune senescent and immune activated CD8 cells were associated with a higher risk of a negative event (relapse, progression, or death) in all studied patients and disease relapse in I-III staged patients. Levels of sCD14 and LPS were higher in patients who will experience a negative event than in patients who will not. In conclusion, in elderly CRC patients higher immunological senescence and immune activation negatively impact the disease outcome; how these characteristics influence the antineoplastic treatments remains to be investigated.
Highlights
In 2018, there were an estimated 140,250 new cases of colorectal cancer (CRC), making it the third most common type of cancer in both men and women [1]
We found that low T-cell receptor rearrangement excision circle (TREC) levels and low telomere length, markers of low thymic function and replicative senescence respectively, are associated with a higher risk of tumor onset [7]
In the present population of cancer patients, in agreement with the previous study, we found that TREC levels decline with age, while telomere length does not
Summary
In 2018, there were an estimated 140,250 new cases of colorectal cancer (CRC), making it the third most common type of cancer in both men and women [1]. CRC was responsible for over 50,000 deaths, leading to an estimated 5-year overall survival (OS) of 64.5% [1]. Age is considered a major risk for solid cancers [2], since cell senescence is associated with oncogene activation, DNA damage accumulation, mitochondrial dysfunction [3] and low-grade chronic inflammation, responsible for age-related diseases [4]. In clinical practice, increasing numbers of elderly patients with CRC undergo surgery and/or receive chemotherapy. These individuals are more likely than young patients to have comorbidities, such as cardiowww.aging-us.com vascular disease, respiratory disease, renal dysfunction, and/or liver dysfunction, lowering the benefit/risk balance compared to younger people [6]
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