Cancer pathogenesis and therapy最新文献

Brain metastases are a leading cause of cancer-related mortality. However, progress in their treatment has been limited over the past decade, due to an incomplete understanding of the underlying biological mechanisms. Employing accurate in vitro and in vivo models to recapitulate the complexities of brain metastasis offers the most promising approach to unravel the intricate cellular and physiological processes involved. Here, we present a comprehensive review of the currently accessible models for studying brain metastasis. We introduce a diverse array of in vitro and in vivo models, including cultured cells using the Transwell system, organoids, microfluidic models, syngeneic models, xenograft models, and genetically engineered models. We have also provided a concise summary of the merits and limitations inherent to each model while identifying the optimal contexts for their effective utilization. This review serves as a comprehensive resource, aiding researchers in making well-informed decisions regarding model selection that align with specific research questions.

Immune checkpoint inhibitors (ICIs) are employed in immunotherapeutic applications for patients with weakened immune systems and can improve the ability of T cells to kill cancer cells. Although ICIs can potentially treat different types of cancers in various groups of patients, their effectiveness may differ among older individuals. The reason ICIs are less effective in older adults is not yet clearly understood, but age-related changes in the immune system, such as immunosenescence and inflammation, may play a role. Therefore, this review focuses on recent advances in understanding the effects of immunosenescence and inflammation on the efficacy of ICIs.

Preimplantation genetic testing (PGT), which was developed as an alternative to prenatal genetic testing, allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus. Originally used for early onset monogenic conditions, PGT is now used to prevent various types of inherited cancer conditions based on the development of PGT technology, assisted reproductive techniques (ARTs), and in vitro fertilization (IVF). This review provides insights into the potential benefits and challenges associated with the application of PGT for hereditary cancer and provides an overview of the existing literature on this test, with a particular focus on the current challenges related to laws, ethics, counseling, and technology. Additionally, this review predicts the future potential applications of this method. Although PGT may be utilized to predict and prevent hereditary cancer, each case should be comprehensively evaluated. The motives of couples must be assessed to prevent the misuse of this technique for eugenic purposes, and non-pathogenic phenotypes must be carefully evaluated. Pathological cases that require this technology should also be carefully considered based on legal and ethical reasoning. PGT may be the preferred treatment for hereditary cancer cases; however, such cases require careful case-by-case evaluations. Therefore, this study concludes that multidisciplinary counseling and support for patients and their families are essential to ensure that PGT is a viable option that meets all legal and ethical concerns.

Background

Immunotherapy favors patients with tumors; however, only 3–26.3% of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors. Combined immunotherapy and chemotherapy has been explored against tumor; however, the combination remains controversial. This study aimed to investigate the tumor immune microenvironment (TIME) and the effects of platinum-based neoadjuvant chemotherapy (NACT) in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy.

Methods

Multiplex immunohistochemistry (IHC) with 11 markers (cluster of differentiation [CD]3, CD8, CD4, CD11c, CD68, forkhead box P3 [Foxp3], programmed cell death 1 [PD-1], programmed cell death 1 ligand 1 [PD-L1], indoleamine 2,3-dioxygenase [IDO], cyclin-dependent kinase inhibitor 2A [p16], and cytokeratin [CK]) was performed to evaluate TIME from 108 matched pre- and post-NACT cervical cancer samples. The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing (RNA-seq) from four paired samples and subsequently verified in 41 samples using IHC.

Results

The infiltration rate of the CD8⁺ T cells in treatment-naive cervical cancer was 0.73%, and those of Foxp3⁺ regulatory T cells (Tregs) and IDO⁺ cells were 0.87% and 17.15%, respectively. Moreover, immunoreactive T cells, dendritic cells, and macrophages were more in the stromal than the intratumor region. NACT increased dendritic, CD3⁺ T, CD8⁺ T, and CD4⁺ T cells and decreased Tregs. The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders. Non-responders primarily showed decreased Tregs and no increase in CD8⁺ T or dendritic cell infiltration. Furthermore, dendritic cells interacted more closely with CD3⁺ T cells after NACT, an effect primarily observed in responders. RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex (MHC) I and MHC II after chemotherapy, validated using IHC.

Conclusions

NACT can reduce Tregs, and when tumor cells are effectively killed, antigen presentation is enhanced, subsequently activating antitumor immunity finitely. Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.

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Conclusions

Background

Methods

Results

Conclusions