RESUMEN

Small nucleolar RNAs (snoRNAs) have robust potential functions and therapeutic value in breast cancer. Herein, we investigated the role SNORA5A in breast cancer. Samples from The Cancer Genome Atlas (TCGA) were reviewed. The transcription matrix and clinical information were analyzed using R software and validated in clinical tissue samples. SNORA5A was significantly down-regulated in breast cancer, and high expression of SNORA5A correlated with a favorable prognosis. High expression of SNORA5A induced a high concentration of tumor-associated macrophages M1 and a low concentration of tumor-associated macrophages M2. Moreover, SNORA5A were clustered in terms related to cancer and immune functions. Possible downstream molecules of SNORA5A were identified, among which TRAF3IP3 was positively correlated with M1 and negatively correlated with M2. The function of TRAF3IP3 in tumor inhibition and its relationship with macrophages in clinical tissue samples were in accordance with bioinformatics analysis results. SNORA5A could regulate macrophage phenotypes through TRAF3IP3 and serves as a potential prognostic marker for breast cancer patients.

RESUMEN

Immunotherapy has changed the course of cancer treatment. The initial steps were made through tumor-specific antibodies that guided the setup of an antitumor immune response. A new and successful generation of antibodies are designed to target immune checkpoint molecules aimed to reinvigorate the antitumor immune response. The cellular counterpart is the adoptive cell therapy, where specific immune cells are expanded or engineered to target cancer cells. In all cases, the key for achieving positive clinical resolutions rests upon the access of immune cells to the tumor. In this review, we focus on how the tumor microenvironment architecture, including stromal cells, immunosuppressive cells and extracellular matrix, protects tumor cells from an immune attack leading to immunotherapy resistance, and on the available strategies to tackle immune evasion.

RESUMEN

In Oral Squamous Cell Carcinomas (OSCC), as in other solid tumors, stromal cells strongly support the spread and growth of the tumor. Macrophages in tumors (tumor-associated macrophages or "TAMs"), can swing between a pro-inflammatory and anti-tumorigenic (M1-like TAMs) state or an anti-inflammatory and pro-tumorigenic (M2-like TAMs) profile depending on the tumor microenvironment cues. Numerous clinical and preclinical studies have demonstrated the importance of macrophages in the prognosis of patients with different types of cancer. Here, our aim was to review the role of M2-like TAMs in the prognosis of patients with OSCC and provide a state of the art on strategies for depleting or reprogramming M2-like TAMs as a possible therapeutic solution for OSCC. The Clinical studies reviewed showed that higher density of CD163+ M2-like TAMs associated with worse survival and that CD206+ M2-TAMs are involved in OSCC progression through epidermal growth factor (EGF) secretion, underlining the important role of CD206 as a marker of OSCC progression and as a therapeutic target. Here, we provide the reader with the current tools, in preclinical and clinical stage, for depleting M2-like TAMs, re-educating them towards M1-like TAMs, and exploiting TAMs as drug delivery vectors.

RESUMEN

PURPOSE: Our study aimed to explore the programmed death 1 (PD-1) expression on tumor-associated macrophage (TAM) in T cell non-Hodgkin lymphoma (T-NHL) and its relationship with lymphoma prognosis. The effect of PD-1 expression on the function of macrophages was also studied. METHODS: Multispectral image quantitative analysis was applied for detecting PD-1 expression on macrophages in T cell lymphoma tissues. The Kaplan-Meier analysis was performed to evaluate the value of PD-1 expression of TAM in predicting the overall survival of T-NHL. PD-1 overexpression THP-1-derived macrophage was constructed and was cocultured with Jurkat cells to explore the effect of PD-1 on macrophage function. RESULTS: In 17 T cell lymphoma cases, the 1-year overall survival rate was significantly lower in patients with higher PD-1 expression on TAMs (0.25 vs 0.86, p < 0.05). After co-cultured with Jurkat cells, classically activated (M1)-related markers on PD-1 overexpressed macrophages were significantly lower than those on controls, while the expressions of alternatively activated (M2) related markers were similar. The PD-1 overexpressed macrophages showed inhibited phagocytosis (4.42% vs 40.7%, p < 0.001) and increased IL-10 secretion (144.48 pg/ml vs 32.32 pg/ml, p < 0.001). CONCLUSION: High PD-1 expression on TAMs in T-NHL may predict poor prognosis. The PD-1 overexpression of macrophages significantly inhibited polarization of M1 macrophages and phagocytosis, and more IL-10 was excreted. These changes may enhance the pro-tumor effects of tumor microenvironment.

Asunto(s)

Linfoma de Células T/metabolismo , Receptor de Muerte Celular Programada 1/biosíntesis , Macrófagos Asociados a Tumores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Células Tumorales Cultivadas

RESUMEN

Cancer is a health issue causing utmost concern and continuing to be one of the leading causes of mortality worldwide. Effective tumor eradication methods that will improve the prognosis and prolong human life are an important topic in modern medicine. Increasing amounts of evidence indicate that the tumor microenvironment plays a significant role in tumor development and migration. Macrophages are important immune cells that commonly infiltrate the tumor microenvironment. Several studies found that macrophages play different roles in the process of cancer development. This article focuses on the tumor microenvironment and the generation, classification, and function of tumor-associated macrophages as well as their significance for tumor immunotherapy and other aspects, it summarizes nearly 10 years of tumor microenvironment and tumor-associated macrophage research, providing a novel insight for tumor immunotherapy.

Asunto(s)

Neoplasias/etiología , Investigación , Microambiente Tumoral/fisiología , Macrófagos Asociados a Tumores/fisiología , Matriz Extracelular/química , Matriz Extracelular/fisiología , Humanos , Inmunoterapia , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia , Neovascularización Patológica/etiología , Células del Estroma/citología , Células del Estroma/fisiología , Escape del Tumor , Microambiente Tumoral/inmunología , Macrófagos Asociados a Tumores/clasificación , Macrófagos Asociados a Tumores/inmunología

RESUMEN

With advances in checkpoint inhibitor and CAR T-cell therapies, among other advances in immunotherapy, this is an exciting time to be a tumor immunologist. We are witnessing the transition of decades of work at the bench leading to substantial success in the clinic. While work continues developing new and improving existing immunotherapies, there remains a great deal of basic tumor immunology still to learn, information that can only lead to greater success in the clinic. One area in need of more attention is understanding the immune response at early stages of breast cancer. While there is no question that early diagnosis and treatment save lives, a greater understanding about the immune response during early stages of breast cancer may reveal information that could assist in monitoring individuals at risk of breast cancer, and could have implications for patients diagnosed at early stages of disease, and may provide important information about the origins of an immune-suppressive environment. Here, we review studies that have looked at the very early immune response to breast cancer focusing on patients with DCIS, before invasion in spontaneous transgenic murine mammary carcinoma models, and before transplantable or orthotopic murine mammary carcinoma models become palpable. The findings revealed that indicators of a pro-tumor immune response are already present at early stages of disease.

Asunto(s)

Carcinoma de Mama in situ/inmunología , Neoplasias de la Mama/inmunología , Tolerancia Inmunológica , Macrófagos Asociados a Tumores/inmunología , Animales , Linfocitos B , Carcinoma de Mama in situ/patología , Enfermedades de la Mama/inmunología , Neoplasias de la Mama/patología , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Humanos , Inmunidad Celular/inmunología , Ratones , Ratones Transgénicos

RESUMEN

Macrophages play an important role in the immune system as a key host defense against pathogens. Non-polarized macrophages can differentiate into pro-inflammatory classical pathway-activated macrophages or anti-inflammatory alternative pathway-activated macrophages, both of which play central roles in breast cancer growth and progression in a process called polarization of macrophages. Classical pathway-activated and alternative pathway-activated macrophages can transform into each other and their transformational properties and orientation are determined by cytokines in the tumor microenvironment. Tumor-associated macrophages display many functions, such as tissue reforming, participating in inflammation and tumor growth in breast cancer progression. Some cytokines, such as interleukins and transcriptional activators, reside in the tumor microenvironment and influence tumor-associated macrophages. Chemotherapy is a common treatment for breast cancer and macrophages play an important role in mammary tumor cell migration, cancer invasion, and angiogenesis. This review summarizes the activities of tumor-associated macrophages in the mammary tumor, chemotherapeutic processes and some potential strategies for breast cancer therapy.

Asunto(s)

Neoplasias de la Mama/etiología , Macrófagos Asociados a Tumores/fisiología , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Polaridad Celular , Femenino , Humanos , Activación de Macrófagos , Microambiente Tumoral

RESUMEN

During tumor development, the spleen acts as an extra-medullar reservoir of LY6Chi inflammatory monocytes, which can migrate toward tumor to differentiate into tumor-associated macrophage (TAMs), renewing the TAM population. In the tumor microenvironment, pro-inflammatory macrophages (M1) acquire anti-inflammatory and pro-tumor (M2) characteristics favoring tumor development. We previously demonstrated that lipoxins, a family of pro-resolving lipid mediators, restored in vitro the cytotoxic M1-like properties of TAMs. Objective: In this study, we have investigated in vivo the cellular mechanisms underlying the anti-tumor property of lipoxins. Methods: Fourteen days after inducing B16-F10 melanoma tumors, mice received one single dose of ATL-1 (1 µg/i.v.), a lipoxin A4 analog. After further 7 days, blood and bone-marrow were collected, tumors and spleens were removed, and TAMs and blood monocytes were isolated. Results: While the population of LY6Chi monocytes was increased in non-treated tumor-bearing mice, the treatment with ATL-1 diminished the population of LY6Chi monocytes in spleen, blood and bone marrow, decreasing macrophage infiltration into the tumor and reducing the M2 markers expression on TAMs. Importantly, those effects were accompanied by an impairment of tumor growth and improved survival of tumor-bearing mice. The data evidence the anti-tumor mechanism of ATL-1, by decreasing the availability of TAM-precursor monocytes and changing TAMs profile in vivo, impairing tumor progression. ATL-1 may become a new tool in cancer control.