Breast cancer (BC) is the most common cancer and the second leading cause of cancer-related deaths in women globally. Despite advancements in treatment strategies, many patients still develop challenging-to-treat metastatic disease. The development and progression of tumors are influenced by genetic/epigenetic changes within tumor cells and alterations in the tumor microenvironment (TME) through a dynamic communication. The TME comprises various elements, including immune, tumor, and stromal cells. Tumor cells at the core of the TME orchestrate complex signals that lead to tumor growth, survival, and resistance to treatment. Human epidermal growth factor receptor 2 (HER2) is overexpressed in a significant proportion of invasive breast cancers, influencing prognosis and prediction. Novel therapeutic approaches target HER2-positive breast cancers by leveraging HER2-targeted therapeuirtcs such as antibody-drug conjugates, monoclonal antibodies, and tyrosine kinase inhibitors. The TME in HER2-positive breast cancers also involves cancer-associated fibroblasts and cancer-associated adipocytes, which play critical roles in tumor progression and therapy resistance. The immune microenvironment also plays a significant role, with studies indicating its impact on outcomes in HER2-positive breast cancer. Trastuzumab, one of the first monoclonal antibodies targeting HER2, has shown promise in enhancing survival rates in HER2-overexpressing breast cancer. Integration of trastuzumab with chemotherapy has demonstrated significant enhancements in disease-free survival as well as overall survival rates during early breast cancer treatment. Trastuzumab functions by inhibiting HER2 signaling pathways, leading to cell cycle arrest and induction of apoptosis. Overall, understanding the complex interplay between HER2, the tumor microenvironment, and therapeutic interventions is essential for improving outcomes in HER2-positive BC.

Invariant natural killer T cells (iNKTs) are innate-type T lymphocytes that directly kill tumor cells or tumor-growth promoting immunosuppressive cells such astumor-associated macrophages. Additionally, iNKTs robustly transactivate the antitumor functions of T, B, natural killer, and dendritic cells as well as reinvigorate exhausted immune cells in the tumor microenvironment. As such, iNKTs make excellent candidates for inclusion in anti-cancer cellular therapies. However, to capitalize on the potential benefits of iNKT cell-based approaches, it is imperative that we develop new and clinically viable strategies to enhance their antitumor function. To that end, two novel monoclonal antibodies (mAbs) that selectively bind to the human (NKTT320) or murine (NKT14m) invariant T cell receptor have been recently developed and characterized. Studies using purified human iNKTs (in vitro) and a model of non-human primate (in vivo) reveal that NKTT320 promotes swift, vigorous and sustained iNKT cell activation that is accompanied by robust production of inflammatory mediators and bystander immune cell activation. Furthermore, NKTT320 augments expression of cytotoxic markers and human iNKT cell degranulation. Similarly, NKT14m prompts dramatic murine iNKT cell activation and functional response both in vitro and in vivo. However, antitumor efficacy of a single dose of NKT14m injection in tumor-bearing mice is limited and tumor-model dependent. In contrast, combination treatment of NKT14m with either low dose interleukin (IL)-12 or the chemotherapeutic agent, cyclophosphamide results in a superior antitumor response in vivo. This is evident by activation of both iNKTs and other immune cells, prolonged survival of the tumor-challenged mice, and long-lasting immunity. Collectively, these recent studies justify further development of anti-iTCR mAbs that can be used alone or in conjunction with immunomodulatory agents to enhance iNKT cell antitumor immunity against various cancers.

Deep learning (DL) is poised to redefine the way medical images are processed and analyzed. Convolutional neural networks (CNNs), a specific type of DL architecture, are exceptional for high-throughput processing, allowing for the effective extraction of relevant diagnostic patterns from large volumes of complex visual data. This technology has garnered substantial interest in the field of neuro-oncology as a promising tool to enhance medical imaging throughput and analysis. A multitude of methods harnessing MRI-based CNNs have been proposed for brain tumor segmentation, classification, and prognosis prediction. They are often applied to gliomas, the most common primary brain cancer, to classify subtypes with the goal of guiding therapy decisions. Additionally, the difficulty of repeating brain biopsies to evaluate treatment response in the setting of often confusing imaging findings provides a unique niche for CNNs to help distinguish the treatment response to gliomas. For example, glioblastoma, the most aggressive type of brain cancer, can grow due to poor treatment response, can appear to grow acutely due to treatment-related inflammation as the tumor dies (pseudo-progression), or falsely appear to be regrowing after treatment as a result of brain damage from radiation (radiation necrosis). CNNs are being applied to separate this diagnostic dilemma. This review provides a detailed synthesis of recent DL methods and applications for intratumor segmentation, glioma classification, and prognosis prediction. Furthermore, this review discusses the future direction of MRI-based CNN in the field of neuro-oncology and challenges in model interpretability, data availability, and computation efficiency.

Given the radiobiological and physical properties of the proton, proton beam therapy has the potential to be advantageous for many patients compared with conventional radiotherapy by limiting toxicity and improving patient outcomes in specific breast cancer scenarios.

Differences in tumor biology and genetic predisposition have been suggested as factors influencing overall survival and increased mortality in Black breast and ovarian cancer patients. Therefore, it is key to evaluate genetic susceptibilities in Afro-Caribbean patients because the black population in the US is not homogeneous. Identifying a high incidence of hereditary breast and ovarian cancer (HBOC) in Afro-Caribbean countries can lead to understanding the pattern of inherited traits in US-Caribbean immigrants and their subsequent generations. The paucity of projects studying the genetic landscape in these populations makes it difficult to design studies aimed at optimizing screening and prophylaxis strategies, which in turn, improve survival and mortality rates. This scoping review identifies and categorizes current research on the genetic paradigm of HBOC in the Afro-Caribbean population. We performed an evaluation of the evidence and generated a summary of findings according to preferred reporting items for systematic review and meta-analysis (PRISMA) Extension for Scoping Reviews guidelines. We included articles that assessed the incidence and prevalence of pathologic germline mutations and experience/barriers for genetic testing in Afro-Caribbean Countries and US-Caribbean patients. Our results highlight countries where genetic landscapes remain severely understudied and support recommending multigene testing in Caribbean-born patients. They highlight a need for further research on the genetic paradigm of HBOC in the Afro-Caribbean population to improve genetic testing/counseling and the subsequent adoption of early detection and risk reduction strategies.

Particulate matter (PM) imposes a significant impact to environmental health with deleterious effects on the human pulmonary and cardiovascular systems. Macrophages (Mφ), key immune cells in lung tissues, have a prominent role in responding to inhaled cells, accommodating inflammation, and influencing tissue repair processes. Elucidating the critical cellular responses of Mφ to PM exposure is essential to understand the mechanisms underlying PM-induced health effects. The present review aims to give a glimpse on literature about the PM interaction with Mφ, triggering the cellular events causing the inflammation, oxidative stress (OS) and tissue damage. The present paper reviews the different pathways involved in Mφ activation upon PM exposure, including phagocytosis, intracellular signaling cascades, and the release of pro-inflammatory mediators. Potential therapeutic strategies targeting Mφ-mediated responses to reduce PM-induced health effects are also discussed. Overall, unraveling the complex interplay between PM and Mφ sheds light on new avenues for environmental health research and promises to develop targeted interventions to reduce the burden of PM-related diseases on global health.

We have witnessed in the last decade new milestones in the treatment of various resistant cancers with new immunotherapeutic modalities. These advances have resulted in significant objective durable clinical responses in a subset of cancer patients. These findings strongly suggested that immunotherapy should be considered for the treatment of all subsets of cancer patients. Accordingly, the mechanisms underlying resistance to immunotherapy must be explored and develop new means to target these resistant factors. One of the pivotal resistance mechanisms in the tumor microenvironment (TME) is the high infiltration of tumor-associated macrophages (TAMs) that are highly immunosuppressive and responsible, in large part, of cancer immune evasion. Thus, various approaches have been investigated to target the TAMs to restore the anti-tumor immune response. One approach is to polarize the M2 TAMS to the M1 phenotype that participates in the activation of the anti-tumor response. In this review, we discuss the various and differential properties of the M1 and M2 phenotypes, the molecular signaling pathways that participate in the polarization, and various approaches used to target the polarization of the M2 TAMs into the M1 anti-tumor phenotype. These approaches include inhibitors of histone deacetylases, PI3K inhibitors, STAT3 inhibitors, TLR agonists, and metabolic reprogramming. Clearly, due to the distinct features of various cancers and their heterogeneities, a single approach outlined above might only be effective against some cancers and not others. In addition, targeting by itself may not be efficacious unless used in combination with other therapeutic modalities.

The prevalence of electronic cigarette use has been declared an epidemic by the U.S. Surgeon General in 2018, particularly among youth aged 18-24 years old. Little is known about the differential use of e-cigarettes by different groups. PubMed, Cochrane, and Google Scholar were used to find relevant articles. A total of 77 articles were included. The extant literature reveals disparities in e-cigarette use by race/ethnicity and sexuality/gender. There are conflicting conclusions regarding disparities by socioeconomic status.