Osteopontin: A Key Multifaceted Regulator in Tumor Progression and Immunomodulation.

The tumor microenvironment (TME) is composed of various cellular components such as tumor cells, stromal cells including fibroblasts, adipocytes, mast cells, lymphatic vascular cells and infiltrating immune cells, macrophages, dendritic cells and lymphocytes. The intricate interplay between these cells influences tumor growth, metastasis and therapy failure. Significant advancements in breast cancer therapy have resulted in a substantial decrease in mortality. However, existing cancer treatments frequently result in toxicity and nonspecific side effects. Therefore, improving targeted drug delivery and increasing the efficacy of drugs is crucial for enhancing treatment outcome and reducing the burden of toxicity. In this review, we have provided an overview of how tumor and stroma-derived osteopontin (OPN) plays a key role in regulating the oncogenic potential of various cancers including breast. Next, we dissected the signaling network by which OPN regulates tumor progression through interaction with selective integrins and CD44 receptors. This review addresses the latest advancements in the roles of splice variants of OPN in cancer progression and OPN-mediated tumor-stromal interaction, EMT, CSC enhancement, immunomodulation, metastasis, chemoresistance and metabolic reprogramming, and further suggests that OPN might be a potential therapeutic target and prognostic biomarker for the evolving landscape of cancer management.

Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer.

Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations.

Lower levels of vitamin D are associated with SARS-CoV-2 infection and mortality in the Indian population: An observational study.

BACKGROUND: The role of vitamin D in the susceptibility and severity of various viral diseases has been well documented. Recently, some reports highlighted the possible importance of vitamin D in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although India receives adequate sunlight throughout the year, the majority of Indians are deficient in vitamin D levels. In the present study, we hypothesized that vitamin D deficiency would be associated with the SARS-CoV-2 infection rate and mortality in the Indian population. MATERIALS AND METHODS: SARS-CoV-2 infection and mortality data were obtained from the Government of India's official website (accessed on 16th August 2020). Various literature databases like PubMed and Google Scholar were searched to find the mean of 25-hydroxyvitamin D [25(OH)D] levels in different states and union territories of India, Pearson correlation was carried out to investigate the possible link between mean 25(OH)D levels and SARS-CoV-2 infection and mortality per million of the population. RESULTS: An inverse correlation was observed between the mean level of 25(OH)D and SARS-CoV-2 infection rate (r = -0.43, p = 0.02) and mortality rate (r = -0.42, p = 0.02). CONCLUSIONS: The present observational study revealed an association of vitamin D with SARS-CoV-2 infection and related mortality. Further studies are required to validate our observations.

ABO blood group system is associated with COVID-19 mortality: An epidemiological investigation in the Indian population.

BACKGROUND: Novel coronavirus disease-19 (COVID-19) has spread worldwide, and to date presence of the virus has been recorded in 215 countries contributing 0.43 million of death. The role of blood groups in susceptibility/resistance to various infectious diseases has been reported. However, the association of blood groups with susceptibility to COVID-19 infections or related death are limited. In the present report, we performed an epidemiological investigation in the Indian population to decipher the importance of blood groups concerning susceptibility or mortality in COVID-19 infection. MATERIALS AND METHODS: Data on COVID-19 infection and mortality was obtained from the website of the Government of India. Prevalence of ABO blood groups in different states and union territories of India were searched using different databases such as PubMed and Google Scholar. Relevant articles were downloaded, and data were extracted. Spearman's rank coefficient analysis was employed to study the correlation between blood group frequencies and COVID-19 infection or mortality rate. RESULTS: A significant inverse correlation was observed between the frequency of O blood group and the COVID-19 mortality rate (Spearman r=-0.36, P=0.03), indicating a possible protective role of O blood group against COVID-19 related death. In contrast, the prevalence of blood group B was positively correlated with COVID-19 death/million (Spearman r=0.67, P<0.0001), suggesting B blood type as a deleterious factor in COVID-19 infection. CONCLUSIONS: ABO blood group system is associated with poor prognosis of COVID-19 infection. Blood group O may protects, and subjects with blood type B could be susceptible to COVID-19 mortality. However, further studies on COVID-19 infected patients in different population are required to validate our findings.