Dataset Information

Interactions between immune challenges and cancer cells proliferation: timing does matter!

ABSTRACT: The immune system is a key component of malignant cell control and it is also involved in the elimination of pathogens that threaten the host. Despite our body is permanently exposed to a myriad of pathogens, the interference of such infections with the immune responses against cancer has been poorly investigated. Through a mathematical model, we show that the frequency, the duration and the action (positive or negative) of immune challenges may significantly impact tumor proliferation. First, we observe that a long immunosuppressive challenge increases accumulation of cancerous cells only if it occurs 14 years after the beginning of immunosenescence. However, short immune challenges result in an even greater accumulation of cancerous cells for the same total duration of immunosuppression. Finally, we show that short challenges of immune activation could lead to a slightly decrease in cancerous cell accumulation compared to a long one. Our results predict that frequent and acute immune challenges could have a different and in some extent higher impact on cancer risk than persistent ones even they have been much less studied in cancer epidemiology. These results are discussed regarding the existing empirical evidences and we suggest potential novel indirect role of infectious diseases on cancer incidence which should be investigated to improve prevention strategies against cancer.

SUBMITTER: Jacqueline C

PROVIDER: S-EPMC5046994 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Copper-mediated cell death presents distinct pathways from established apoptosis processes, suggesting alternative therapeutic approaches for colon cancer. Our research aims to develop a predictive framework utilizing long-noncoding RNAs (lncRNAs) related to cuproptosis to predict colon cancer outcomes while examining immune interactions and intercellular signaling. We obtained colon cancer-related human mRNA expression profiles and clinical information from the Cancer Genome Atlas repository. To isolate lncRNAs involved in cuproptosis, we applied Cox proportional hazards modeling alongside the least absolute shrinkage and selection operator technique. We elucidated the underlying mechanisms by examining the tumor mutational burden, the extent of immune cell penetration, and intercellular communication dynamics. Based on the model, drugs were predicted and validated with cytological experiments. A 13 lncRNA-cuproptosis-associated risk model was constructed. Two colon cancer cell lines were used to validate the predicted representative mRNAs with high correlation coefficients with copper-induced cell death. Survival enhancement in the low-risk cohort was evidenced by the trends in Kaplan-Meier survival estimates. Analysis of immune cell infiltration suggested that survival was induced by the increased infiltration of naïve CD4+ T cells and a reduction of M2 macrophages within the low-risk faction. Decreased infiltration of naïve B cells, resting NK cells, and M0 macrophages was significantly associated with better overall survival. Combined single-cell analysis suggested that CCL5-ACKR1, CCL2-ACKR1, and CCL5-CCR1 pathways play key roles in mediating intercellular dialogues among immune constituents within the neoplastic microhabitat. We identified three drugs with a high sensitivity in the high-risk group. In summary, this discovery establishes the possibility of using 13 cuproptosis-associated lncRNAs as a risk model to assess the prognosis, unravel the immune mechanisms and cell communication, and improve treatment options, which may provide a new idea for treating colon cancer.

Dataset Information

Interactions between immune challenges and cancer cells proliferation: timing does matter!

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets