Update on the challenges and recent advances in cancer immunotherapy

Baronzio, Gianfranco; Parmar, Gurdev; Шубина, И. Ж.; Cassutti, Valter; Giuli, Sergio; Ballerini, Marco; Kiselevsky, M. V.

doi:10.2147/itt.s30818

Cited by 8 publications

(2 citation statements)

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“…The hallmark of these effects is the acquisition of a senescence-associated secretory phenotype that turns senescent fibroblasts into proinflammatory cells with the ability to promote tumor progression [13]. Concomitantly, many other factors favor cancer development in older patients, such as decreased apoptosis, micro-environmental damages, chromosomal instability and exposure to carcinogens [14]. However, a full understanding of the aging process is far from complete with many open questions currently under investigation [15].…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in the BACH2 and PRDM1 genes in lymphocytes from healthy donors and chronic lymphocytic leukemia patients

et al. 2019

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BackgroundAge-related genetic changes in lymphocyte subsets are not currently well documented. BACH2 is a transcription factor that plays an important role in immune-mediated homeostasis by tightly regulating PRDM1 expression in both B-cells and T-cells. BACH2 gene expression is highly sensitive to DNA damage in aged mice. This concept led us to investigate the variation in BACH2 and also PRDM1 expression in major lymphocyte subsets with age.MethodsLymphocyte subsets from 60 healthy donors, aged from 20 to 90 years, and 41 untreated chronic lymphocytic leukemia patients were studied. BACH2 and PRDM1 gene expression was analyzed by real-time quantitative PCR. BACH2 gene expression was correlated with its protein expression. Lymphocyte apoptosis was evaluated after intracellular oxidative stress-inducing etoposide treatment of T and B cells.ResultsOur analysis shows BACH2 mRNA downregulation with age in healthy donor CD4+, CD8+ T-cells and CD19+ B-cells. Decreased BACH2 expression was also correlated with an age-related reduction in CD8 + CD28+ T-cells. We found a strong correlation between age-related BACH2 downregulation and decreased CD4+ T-cell and CD19+ B-cell apoptosis. PRDM1, as expected, was significantly upregulated in CD4+ T-cells, CD8+ T-cells and CD19+ B-cells, and inversely correlated with BACH2. A comparison of untreated chronic lymphocytic leukemia patients with age-matched healthy donors reveals that BACH2 mRNA expression was further reduced in CD4+ T-cells, CD8+ T-cells and leukemic-B cells. PRDM1 gene expression was consequently significantly upregulated in CD4+ and CD8+ T-cells in chronic lymphocytic leukemia patients but not in their leukemic B-cells.ConclusionOverall, our data suggest that BACH2 and PRDM1 genes are significantly correlated with age in human immune cells and may be involved in immunosenescence.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5276-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Age-related changes in the BACH2 and PRDM1 genes in lymphocytes from healthy donors and chronic lymphocytic leukemia patients

et al. 2019

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“…With the development of drug-carrying nanotechnology, significantly more antitumor molecules such as antibodies, molecular vaccines, and cytokines can be selectively delivered to target sites for augmenting retention (Bertrand et al, 2014 ); this is assisted by folate-, transferrin-, mannose-, and antibody-conjugated nanomaterials (Huang et al, 2016 ) and is combined with the EPR effect. The discovery of new drugs such as ipilimumab has paved the way for active immunotherapy by eliminating residuals and advanced cancer with durable and long-lasting responses (Hodi et al, 2010 ; Baronzio et al, 2013 ).…”

Section: Enhancement Of Cancer Immunotherapymentioning

confidence: 99%

Tumor Immune Microenvironments (TIMEs): Responsive Nanoplatforms for Antitumor Immunotherapy

et al. 2020

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Interest in cancer immunotherapy has rapidly risen since it offers many advantages over traditional approaches, such as high efficiency and prevention of metastasis. Efforts have primarily focused on two major strategies for regulating the body's antitumor immune response mechanisms: “enhanced immunotherapy” that aims to amplify the immune activation, and “normalized immunotherapy” that corrects the defective immune mechanism in the tumor immune microenvironments (TIMEs), which returns to the normal immune trajectory. However, due to the complexity and heterogeneity of the TIMEs, and lack of visualization research on the immunotherapy process, cancer immunotherapy has not been widely used in clinical setting. Recently, through the design and modification of nanomaterials, intelligent TIME-responsive nanoplatforms were developed from which encouraging results in many aspects of immunotherapy have been achieved. In this mini review, the status of designed nanomaterials for nanoplatform-based immune regulation of TIMEs has been emphasized, particularly with respect to the aforementioned approaches. It is envisaged that future prospects will focus on a combination of multiple immunotherapies for more efficient cancer inhibition and elimination.

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