Don't eat me/eat me signals as a novel strategy in cancer immunotherapy.

Cancer stands as one of the prominent global causes of death, with its incidence burden continuously increasing, leading to a substantial rise in mortality rates. Cancer treatment has seen the development of various strategies, each carrying its drawbacks that can negatively impact the quality of life for cancer patients. The challenge remains significant within the medical field to establish a definitive cancer treatment that minimizes complications and limitations. In the forthcoming years, exploring new strategies to surmount the failures in cancer treatment appears to be an unavoidable pursuit. Among these strategies, immunology-based ones hold substantial promise in combatting cancer and immune-related disorders. A particular subset of this approach identifies "eat me" and "Don't eat me" signals in cancer cells, contrasting them with their counterparts in non-cancerous cells. This distinction could potentially mark a significant breakthrough in treating diverse cancers. By delving into signal transduction and engineering novel technologies that utilize distinct "eat me" and "Don't eat me" signals, a valuable avenue may emerge for advancing cancer treatment methodologies. Macrophages, functioning as vital components of the immune system, regulate metabolic equilibrium, manage inflammatory disorders, oversee fibrosis, and aid in the repair of injuries. However, in the context of tumor cells, the overexpression of "Don't eat me" signals like CD47, PD-L1, and beta-2 microglobulin (B2M), an anti-phagocytic subunit of the primary histocompatibility complex class I, enables these cells to evade macrophages and proliferate uncontrollably. Conversely, the presentation of an "eat me" signal, such as Phosphatidylserine (PS), along with alterations in charge and glycosylation patterns on the cellular surface, modifications in intercellular adhesion molecule-1 (ICAM-1) epitopes, and the exposure of Calreticulin and PS on the outer layer of the plasma membrane represent universally observed changes on the surface of apoptotic cells, preventing phagocytosis from causing harm to adjacent non-tumoral cells. The current review provides insight into how signaling pathways and immune cells either stimulate or obstruct these signals, aiming to address challenges that may arise in future immunotherapy research. A potential solution lies in combination therapies targeting the "eat me" and "Don't eat me" signals in conjunction with other targeted therapeutic approaches. This innovative strategy holds promise as a novel avenue for the future treatment of cancer.

Immune checkpoints and their promising prospect in cholangiocarcinoma treatment in combination with other therapeutic approaches.

Cholangiocarcinoma (CCA) is one of the malignant tumors that has shown rapid development in incidence and mortality in recent years. Like other types of cancer, patients with CCA experience alterations in the expression of immune checkpoints, indicating the importance of immune checkpoint inhibitors in treating CCA. The results of TCGA analysis in this study revealed a marginal difference in the expression of important immune checkpoints, Programmed cell death 1 (PD-1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and their ligands in CCA samples compared to normal ones. This issue showed the importance of combination therapy in this cancer. This review considers CCA treatment and covers several therapeutic modalities or combined treatment strategies. We also cover the most recent developments in the field and outline the important areas of immune checkpoint molecules as prognostic variables and therapeutic targets in CCA.

Out-of-pocket payments for treatment of COVID-19 in Iran.

INTRODUCTION: Out-of-pocket (OOP) is among the payment methods in Iran's health system. The present study aimed to examine the OOP treatment costs for patients with COVID-19 in Iran. METHODS: A descriptive-analytical, cross-sectional study was conducted in 2021. In this study, the cost records of 550 patients with COVID-19 hospitalized in a referral center of COVID-19 were selected using the stratified random sampling method. The required data were collected using a researcher-made questionnaire. Data were analyzed by t-test, ANOVA, and Pearson's correlation coefficient in SPSS software version 23 at p = 0.05. RESULTS: The total direct costs were 1,037,992.15 US $. Moreover, the shares of patients (OOP), basic insurance, government subsidy, supplementary insurance, discounts, and out-of-government subsidy in the total direct costs were US $ 92,231.21, 746,932.99 US $, 155,127.08 US $, 39,690.25 US $ and 4010.61 US $, respectively. In addition, the results confirmed that there was a positive and significant relationship between the patients' OOP payments and the length of stay. It also found that the patients' OOP payments are subject to the type of insurance program and discharge method. CONCLUSION: According to the results, 8.89% of the total direct costs were directly paid out of the patients' pockets. The research findings confirm the urgent need to make decisions and implement effective interventions for COVID-19 disease by controlling risk factors and exploiting other countries' successful experiences and international organizations' recommendations to decrease the prevalence of the infected and consequently reduce the financial pressure of the disease on patients by approving the expansion of the insurance organizations' role.