T Cell Aging in Patients with Colorectal Cancer—What Do We Know So Far?

Thoma, Oana‐Maria; Neurath, Markus F.; Waldner, Maximilian J.

doi:10.3390/cancers13246227

Cited by 8 publications

(6 citation statements)

References 113 publications

(159 reference statements)

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“…The widespread functional inactivation of p53 and RB results in G1/S checkpoint defects of the cell cycle and continuous accumulation of DNA damage ( 7 ), causing cell cycle arrest, resulting in decreased cell proliferation. In addition, exhausted T cells were characterized by high expression of CD45RA and C-C chemokine receptor type 7 (CCR7), and naive cells turn into effector memory T cells ( 8 ) CD27/CD28 costimulatory molecules on the surface of T cells are consistently low in expression. CD27 is an important molecule for T cells to maintain immunity, CD28 is an important second signal in T cell activation, and loss of CD27 and CD28 will lead to reduced immune capacity ( 9 ).…”

Section: T Cell Senescencementioning

confidence: 99%

T cell senescence: a new perspective on immunotherapy in lung cancer

Huang,

Wang,

Fang

et al. 2024

Front. Immunol.

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T cell senescence is an indication of T cell dysfunction. The ability of senescent T cells to respond to cognate antigens is reduced and they are in the late stage of differentiation and proliferation; therefore, they cannot recognize and eliminate tumor cells in a timely and effective manner, leading to the formation of the suppressive tumor microenvironment. Establishing methods to reverse T cell senescence is particularly important for immunotherapy. Aging exacerbates profound changes in the immune system, leading to increased susceptibility to chronic, infectious, and autoimmune diseases. Patients with malignant lung tumors have impaired immune function with a high risk of recurrence, metastasis, and mortality. Immunotherapy based on PD-1, PD-L1, CTLA-4, and other immune checkpoints is promising for treating lung malignancies. However, T cell senescence can lead to low efficacy or unsuccessful treatment results in some immunotherapies. Efficiently blocking and reversing T cell senescence is a key goal of the enhancement of tumor immunotherapy. This study discusses the characteristics, mechanism, and expression of T cell senescence in malignant lung tumors and the treatment strategies.

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Section: T Cell Senescencementioning

confidence: 99%

T cell senescence: a new perspective on immunotherapy in lung cancer

Huang,

Wang,

Fang

et al. 2024

Front. Immunol.

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“…They play an essential role in the pathogenesis and progression of CRC (45), mainly including helper CD4 + T cells and cytotoxic CD8 + T cells. The differences in the activation status and types of T cells may be closely related to the prognosis of CRC patients (46)(47)(48). The activation of CD4 + T cells by antigen-presenting cells promotes the migration of highly cytotoxic CD8 + T cells to the tumor site and plays the role of tumor immune mediators (49).…”

Section: T Cellsmentioning

confidence: 99%

“…The activation of CD4 + T cells by antigen-presenting cells promotes the migration of highly cytotoxic CD8 + T cells to the tumor site and plays the role of tumor immune mediators (49). Exhausted CD8 + T cells have abundant high expansion potential in TME (48). As a common metabolite, lactate can be rapidly produced by both tumor cells and activated T cells, but its function is not unchanged.…”

Section: T Cellsmentioning

confidence: 99%

Lactate-related metabolic reprogramming and immune regulation in colorectal cancer

Sun

Zhu

et al. 2023

Front. Endocrinol.

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Changes in cellular metabolism involving fuel sources are well-known mechanisms of cancer cell differentiation in the context of carcinogenesis. Metabolic reprogramming is regulated by oncogenic signaling and transcriptional networks and has been identified as an essential component of malignant transformation. Hypoxic and acidified tumor microenvironment contributes mainly to the production of glycolytic products known as lactate. Mounting evidence suggests that lactate in the tumor microenvironment of colorectal cancer(CRC) contributes to cancer therapeutic resistance and metastasis. The contents related to the regulatory effects of lactate on metabolism, immune response, and intercellular communication in the tumor microenvironment of CRC are also constantly updated. Here we summarize the latest studies about the pleiotropic effects of lactate in CRC and the clinical value of targeting lactate metabolism as treatment. Different effects of lactate on various immune cell types, microenvironment characteristics, and pathophysiological processes have also emerged. Potential specific therapeutic targeting of CRC lactate metabolism is also discussed. With increased knowledge, effective druggable targets might be identified, with the aim of improving treatment outcomes by reducing chemoresistance.

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“…CRC is a malignancy originating from large intestinal tissue, including the colon and rectum, which is often associated with the aging process, especially T cell dysfunction involving telomere defects and telomerase activity. 4 According to the American Cancer Society, CRC is ranked third for the highest number of cases and fourth for cancer-related deaths.…”

Section: Introductionmentioning

confidence: 99%

The Association Between CYP24A1 rs4809957 Gene Polymorphism and Grade of Colorectal Cancer at Prof. Dr. I G.N.G Ngoerah Hospital in Bali

Puspitasari,

Dewi,

Artini

et al. 2023

International Journal of Scientific Advances

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Introduction: Colorectal cancer (CRC) is a malignancy in the large intestine, including the colon and rectum. One of the pathogenesis of CRC is the molecular pathway. This study aimed to evaluate the association between the CYP24A1 rs4809957 gene polymorphism and the histopathological grade of CRC patients at Prof. Dr. I G.N.G. Ngoerah Hospital in 2018-2019. Methods: This research was an observational analytic study with a cross-sectional design. This study used 34 samples of stored biological material from CRC tissue. CYP24A1 polymorphism (rs4809957) was identified using qPCR. Results: The results showed that the mean ± SD of the patient’s age was 61.09 ± 11.79 years. A total of 18 patients (52.9%) of the patient sample were male, and 16 patients (47.1%) were female. The histopathological grade of CRC in this study consisted of 30 samples (88.2%) of low grade and 4 (11.8%) of high grade. There were 21 patients (61.8%) who had a history of smoking. In addition, 20 patients (58.8%) had a history of consuming alcoholic beverages. This study’s CYP24A1 rs4809957 gene polymorphism comprised the AA+AG genotype in 23 samples (67.6%) and GG in 11 (32.4%). There was no significant association between the CYP24A1 rs4809957 gene polymorphism and the histopathological grade of CRC with a p-value = 0.580 and PR (95%CI) = 2.33 (0.83 – 19.42). Conclusion: This study concluded that there was no significant association between the CYP24A1 rs4809957 gene polymorphism and the histopathological grade of CRC patients.

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T Cell Aging in Patients with Colorectal Cancer—What Do We Know So Far?

Cited by 8 publications

References 113 publications

T cell senescence: a new perspective on immunotherapy in lung cancer

T cell senescence: a new perspective on immunotherapy in lung cancer

Lactate-related metabolic reprogramming and immune regulation in colorectal cancer

The Association Between CYP24A1 rs4809957 Gene Polymorphism and Grade of Colorectal Cancer at Prof. Dr. I G.N.G Ngoerah Hospital in Bali

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