Memory T cells: strategies for optimizing tumor immunotherapy

Telomerase is a reverse transcriptase that maintains telomeres length, compensating for the attrition of chromosomal ends that occurs during each replication cycle. Telomerase is expressed in germ cells and stem cells, whereas it is virtually undetectable in adult somatic cells. On the other hand, telomerase is broadly expressed in the majority of human tumors playing a crucial role in the replicative behavior and immortality of cancer cells. Several studies have demonstrated that telomerase-derived peptides are able to bind to HLA (human leukocyte antigen) class I and class II molecules and effectively activate both CD8+ and CD4+ T cells subsets. Due to its broad and selective expression in cancer cells and its significant immunogenicity, telomerase is considered an ideal universal tumor-associated antigen, and consequently, a very attractive target for anti-cancer immunotherapy. To date, different telomerase targeting immunotherapies have been studied in pre-clinical and clinical settings, these approaches include peptide vaccination and cell-based vaccination. The objective of this review paper is to discuss the role of human telomerase in cancer immunotherapy analyzing recent developments and future perspectives in this field.

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“…Improve functional characteristics of the induced lymphocytes (e.g., memory T cells) [115,116,120,121] Tumor microenvironment…”

Section: Discussionmentioning

confidence: 99%

Anti-Cancer Immunotherapies Targeting Telomerase

Negrini

Palma

Filaci

2020

Cancers

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“…Based on their function and phenotypical features, memory T cell subsets may be classically divided into central memory T cells and effector memory T cells 53,54 . Nonetheless, additional memory subsets have been revealed.…”

Section: Autophagy Regulates T Cell Memorymentioning

confidence: 99%

“…Many molecular and metabolic regulation mechanisms are involved in memory T cell formation. The relative hot spots, such as cytokines (IL‐15, IL‐7, IL‐10, IL‐21 53 ), T‐cell costimulatory molecules (OX40 and CD28 56 ) and transcriptional factors (eomesodermin, Bcl6, Foxo1 and Lef1 53,56 ), have been studied extensively in the past. However, how autophagy influences T cell memory attracts less attention than the cytokines and transcription factors.…”

Section: Autophagy Regulates T Cell Memorymentioning

confidence: 99%

Autophagy in T‐cell differentiation, survival and memory

Wang

Das

Kumar

et al. 2020

Immunol. Cell Biol.

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Over the past decade, autophagy has emerged as a critical regulatory mechanism of the immune system through critically controlling various aspects of T cell biology and determining the fate of different T cell subsets. Autophagy maintains T cell development and survival by regulating the degradation of organelles and apoptotic proteins. The autophagic process also impacts the formation of memory T cells. Alteration of autophagy in T cells may lead to a variety of pathological conditions such as inflammation, autoimmune diseases and cancer. In this review, we discuss how autophagy impacts T cell differentiation, survival and memory, and its implication in immunotherapy for various diseases.

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“…A subset of memory cells remains long term in secondary lymphoid organs or in the tumor bed. It has been widely reported that the individual patient’s T cell profile has an impact on adoptive T cell therapy efficacy [ 8 , 9 ]: chronic antigen exposure and stimulation imposed by cancer leads to the accumulation of terminally differentiated effector T cells, while the memory phenotype is more desirable due to its enhanced persistence and increased activity [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic versus Solid Cancers and T Cell Dysfunction: Looking for Similarities and Distinctions

Montironi

Muñoz-Pinedo

Eldering

2021

Cancers

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Cancer cells escape, suppress and exploit the host immune system to sustain themselves, and the tumor microenvironment (TME) actively dampens T cell function by various mechanisms. Over the last years, new immunotherapeutic approaches, such as adoptive chimeric antigen receptor (CAR) T cell therapy and immune checkpoint inhibitors, have been successfully applied for refractory malignancies that could only be treated in a palliative manner previously. Engaging the anti-tumor activity of the immune system, including CAR T cell therapy to target the CD19 B cell antigen, proved to be effective in acute lymphocytic leukemia. In low-grade hematopoietic B cell malignancies, such as chronic lymphocytic leukemia, clinical outcomes have been tempered by cancer-induced T cell dysfunction characterized in part by a state of metabolic lethargy. In multiple myeloma, novel antigens such as BCMA and CD38 are being explored for CAR T cells. In solid cancers, T cell-based immunotherapies have been applied successfully to melanoma and lung cancers, whereas application in e.g., breast cancer lags behind and is modestly effective as yet. The main hurdles for CAR T cell immunotherapy in solid tumors are the lack of suitable antigens, anatomical inaccessibility, and T cell anergy due to immunosuppressive TME. Given the wide range of success and failure of immunotherapies in various cancer types, it is crucial to comprehend the underlying similarities and distinctions in T cell dysfunction. Hence, this review aims at comparing selected, distinct B cell-derived versus solid cancer types and at describing means by which malignant cells and TME might dampen T cell anti-tumor activity, with special focus on immunometabolism. Drawing a meaningful parallel between the efficacy of immunotherapy and the extent of T cell dysfunction will shed light on areas where we can improve immune function to battle cancer.

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Memory T cells: strategies for optimizing tumor immunotherapy

Cited by 155 publications

References 143 publications

Anti-Cancer Immunotherapies Targeting Telomerase

Anti-Cancer Immunotherapies Targeting Telomerase

Autophagy in T‐cell differentiation, survival and memory

Hematopoietic versus Solid Cancers and T Cell Dysfunction: Looking for Similarities and Distinctions

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