Immune Aging and Immunotherapy in Cancer

Kaiser, Melanie; Semeraro, Maria Donatella; Herrmann, Markus; Absenger, Gudrun; Gerger, Armin; Renner, Wilfried

doi:10.3390/ijms22137016

Cited by 37 publications

(35 citation statements)

References 148 publications

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“…However, a large amount of clinical evidence suggests that CBI therapy remains effective even in patients over the age of 75 and similar clinical response has been observed when patients are stratified by age (59,60). For instance, response to CBI immunotherapy has been found to be independent of age in patients affected with IV stage melanoma and treated with anti-CTLA4 (61).…”

Section: Tcr Repertoire Diversity and Patients' Response To Cbimentioning

confidence: 87%

Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

Cardinale¹,

Compagnucci²,

Locatelli³

et al. 2021

Front. Immunol.

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The capacity of T cells to recognize and mount an immune response against tumor antigens depends on the large diversity of the T-cell receptor (TCR) repertoire generated in the thymus during the process of T-cell development. However, this process is dramatically impaired by immunological insults, such as that caused by cytoreductive cancer therapies and infections, and by the physiological decline of thymic function with age. Defective thymic function and a skewed TCR repertoire can have significant clinical consequences. The presence of an adequate pool of T cells capable of recognizing specific tumor antigens is a prerequisite for the success of cancer immunotherapy using checkpoint blockade therapy. However, while this approach has improved the chances of survival of patients with different types of cancer, a large proportion of them do not respond. The limited response rate to checkpoint blockade therapy may be linked to a suboptimal TCR repertoire in cancer patients prior to therapy. Here, we focus on the role of the thymus in shaping the T-cell pool in health and disease, discuss how the TCR repertoire influences patients’ response to checkpoint blockade therapy and highlight approaches able to manipulate thymic function to enhance anti-tumor immunity.

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Section: Tcr Repertoire Diversity and Patients' Response To Cbimentioning

confidence: 87%

Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

Cardinale¹,

Compagnucci²,

Locatelli³

et al. 2021

Front. Immunol.

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show abstract

Section: Discussionmentioning

confidence: 99%

“…Lymphocyte exhaustion can be defined as the progressive loss of functionalities and a reduced proliferative capability triggered by chronic antigen stimulation due to chronic infections or cancers [1]. Anergy in lymphocytes is a functionally defined state of hyporesponsiveness in which lymphocytes do not proliferate and have defective production of major growth factors and/or inflammatory cytokines following an antigen encounter and subsequent receptor–ligand ligation [1]. Cellular senescence is a permanent G1 cell cycle arrest that restricts the life span of cells to control cell replication, as a result of oncogene activation, deoxyribonucleic acid (DNA) telomere degradation, epigenomic changes, or stressful stimuli including reactive oxygen species, ionizing radiation or certain chemicals [1].…”

Section: Discussionmentioning

confidence: 99%

NK‐cell exhaustion, B‐cell exhaustion and T‐cell exhaustion—the differences and similarities

Roe¹

2022

Immunology

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T-cell exhaustion has been extensively researched, compared with B-cell exhaustion and NK-cell exhaustion, which have received considerably less attention; and there is less of a consensus on the precise definitions of NK-cell and B-cell exhaustion. NKcell exhaustion, B-cell exhaustion and T-cell exhaustion are examples of lymphocyte exhaustion, and they have several differences and similarities. Lymphocyte exhaustion is also frequently confused with anergy, cellular senescence and suppression, because these conditions can have significant overlapping similarities with exhaustion. An additional source of confusion is due to the fact that lymphocyte exhaustion is not a binary state, but instead has a spectrum of severity induced by different levels and duration of continuous antigenic stimulation. Concurrent multiple types of lymphocyte exhaustion are possible, and this situation is herein called poly-lymphocyte exhaustion. Poly-lymphocyte exhaustion for the same cancer or pathogen would be especially dangerous. As there are significant advantages for a pathogen by inducing poly-lymphocyte exhaustion in an immune system, there are pathogens with an evolved capability to induce poly-lymphocyte exhaustion. These pathogens may include certain manipulative viruses, bacteria, fungi and protozoan parasites.

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“…This would be in concordance with the idea that more diversified TCR repertoires increase the likelihood of tumour antigens recognition. However, clinical data from other studies reveal that there are no differences between young and old patients responding to ICI therapies [ 138 , 139 , 140 ].…”

Section: The Tcr Repertoire As a Predictive Biomarker Of Immune Check...mentioning

confidence: 99%

Evaluation of the TCR Repertoire as a Predictive and Prognostic Biomarker in Cancer: Diversity or Clonality?

Aran

Garrigós²,

Curigliano

et al. 2022

Cancers

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T cells play a vital role in the anti-tumoural response, and the presence of tumour-infiltrating lymphocytes has shown to be directly correlated with a good prognosis in several cancer types. Nevertheless, some patients presenting tumour-infiltrating lymphocytes do not have favourable outcomes. The TCR determines the specificities of T cells, so the analysis of the TCR repertoire has been recently considered to be a potential biomarker for patients’ progression and response to therapies with immune checkpoint inhibitors. The TCR repertoire is one of the multiple elements comprising the immune system and is conditioned by several factors, including tissue type, tumour mutational burden, and patients’ immunogenetics. Its study is crucial to understanding the anti-tumoural response, how to beneficially modulate the immune response with current or new treatments, and how to better predict the prognosis. Here, we present a critical review including essential studies on TCR repertoire conducted in patients with cancer with the aim to draw the current conclusions and try to elucidate whether it is better to encounter higher clonality with few TCRs at higher frequencies, or higher diversity with many different TCRs at lower frequencies.

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Immune Aging and Immunotherapy in Cancer

Cited by 37 publications

References 148 publications

Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

Thymic Function and T-Cell Receptor Repertoire Diversity: Implications for Patient Response to Checkpoint Blockade Immunotherapy

NK‐cell exhaustion, B‐cell exhaustion and T‐cell exhaustion—the differences and similarities

Evaluation of the TCR Repertoire as a Predictive and Prognostic Biomarker in Cancer: Diversity or Clonality?

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