The alteration of glucose metabolism is one of the first biochemical characteristics associated with cancer cells since most of these cells increase glucose consumption and glycolytic rates even in the presence of oxygen, which has been called “aerobic glycolysis” or the Warburg effect. Human papillomavirus (HPV) is associated with approximately 5% of all human cancers worldwide, principally to cervical cancer. E6 and E7 are the main viral oncoproteins which are required to preserve the malignant phenotype. These viral proteins regulate the cell cycle through their interaction with tumor suppressor proteins p53 and pRB, respectively. Together with the viral proteins E5 and E2, E6 and E7 can favor the Warburg effect and contribute to radio- and chemoresistance through the increase in the activity of glycolytic enzymes, as well as the inhibition of the Krebs cycle and the respiratory chain. These processes lead to a fast production of ATP obtained by Warburg, which could help satisfy the high energy demands of cancer cells during proliferation. In this way HPV proteins could promote cancer hallmarks. However, it is also possible that during an early HPV infection, the Warburg effect could help in the achievement of an efficient viral replication.

Characterization of cervical cancer stem cell-like cells: phenotyping, stemness, and Human Papilloma Virus co-receptor expression

Cancer stem cell impact on clinical oncology

Cross talk between cancer cells and the immune system is determinant for cancer progression. Emerging evidence demonstrates that GC characteristics such as metastasis, treatment resistance, and disease recurrence are associated with a tumor subpopulation called gastric cancer stem cells (GCSCs). However, the specific interaction between GCSCs and the immune microenvironment is still under investigation. Although immune evasion has been well described for cancer stem cells (CSCs), recent studies show that GCSCs can also regulate the immune system and even benefit from it. This review will provide an overview of bidirectional interactions between CSCs and immune cells in GC, compiling relevant data about how CSCs can induce leukocyte reprogramming, resulting in pro-tumoral immune cells that orchestrate promotion of metastasis, chemoresistance, tumorigenicity, and even increase in number of cancer cells with stem properties. Some immune cells studied are tumor-associated macrophages (TAMs), neutrophils, Th17 and T regulatory (T_reg) cells, mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs), as well as the signaling pathways involved in these pro-tumoral activities. Conversely, although there are cytotoxic leukocytes that can potentially eliminate GCSCs, we describe mechanisms for immune evasion in GCSCs and their clinical implications. Furthermore, we describe current available immunotherapy targeting GCSC-related markers as possible treatment for GC, discussing how the CSC-modified immune microenvironment can mitigate or inactivate these immunotherapies, limiting their effectiveness. Finally, we summarize key concepts and relevant evidence to understand the cross talk between GCSCs and the immune microenvironment as an important process for effective design of therapies against GCSCs that improve the outcome of patients with GC.

Cancer Stem Cells (CSCs) are highly tumorigenic, chemoresistant, and immune evasive. They emerge as a central driver that gives rise to the bulk of tumoral mass, modifies the tumor microenvironment (TME), and exploits it, leading to poor clinical outcomes for patients with cancer. The existence of CSCs thus accounts for the failure of conventional therapies and immune surveillance. Identifying CSCs in solid tumors remains a significant challenge in modern oncology, with the use of cell surface markers being the primary strategy for studying, isolating, and enriching these cells. In this review, we explore CSC markers, focusing on the underlying signaling pathways that drive CSC self-renewal, which simultaneously makes them intrinsically chemoresistant and immune system evaders. We comprehensively discuss the autonomous and non-autonomous functions of CSCs, with particular emphasis on their interactions with the tumor microenvironment, especially immune cells. This reciprocal network enhances CSCs malignancy while compromising the surrounding niche, ultimately defining therapeutic vulnerabilities associated with each CSC marker. The most common CSCs surface markers addressed in this review-CD44, CD133, ICAM1/CD54, and LGR5-provide insights into the interplay between chemoresistance and immune evasion, two critically important phenomena in disease eradication. This new perspective on the state-of-the-art of CSCs will undoubtedly open new avenues for therapy.

Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the United States. The prostate-specific antigen (PSA), often found at high levels in the serum of PCa patients, has been used as a marker for PCa detection and as a target of immunotherapy. The murine IgG1 monoclonal antibody AR47.47, specific for human PSA, has been shown to enhance antigen presentation by human dendritic cells and induce both CD4 and CD8 T-cell activation when complexed with PSA. In this study, we explored the properties of a novel mouse/human chimeric anti-PSA IgE containing the variable regions of AR47.47 as a potential therapy for PCa. Our goal was to take advantage of the unique properties of IgE in order to trigger immune activation against PCa.