Principal Investigator- Dr. Soumen Basak https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/53 2026-04-27T15:59:13Z 2026-04-27T15:59:13Z Soumen Basak Anwesha Kar Debaleena Bhowmik Anupam Gautam Debashree Basak Ishita Sarkar Puspendu Ghosh Deborpita Sarkar Alvina Deka Paramita Chakraborty Asima Mukhopadhyay Shikhar Mehrotra Snehanshu Chowdhury Sandip Paul Shilpak Chatterjee https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1501 2025-12-05T12:41:51Z 2022-01-01T00:00:00Z

Title: Intracellular Acetyl CoA Potentiates the Therapeutic Efficacy of Antitumor CD8+ T Cells Authors: Soumen Basak; Anwesha Kar; Debaleena Bhowmik; Anupam Gautam; Debashree Basak; Ishita Sarkar; Puspendu Ghosh; Deborpita Sarkar; Alvina Deka; Paramita Chakraborty; Asima Mukhopadhyay; Shikhar Mehrotra; Snehanshu Chowdhury; Sandip Paul; Shilpak Chatterjee Abstract: Effector CD8+ T cells rely primarily on glucose metabolism to meet their biosynthetic and functional needs. However, nutritional limitations in the tumor microenvironment can cause T-cell hyporesponsiveness. Therefore, T cells must acquire metabolic traits enabling sustained effector function at the tumor site to elicit a robust antitumor immune response. Here, we report that IL12-stimulated CD8+ T cells have elevated intracellular acetyl CoA levels and can maintain IFNγ levels in nutrient-deprived, tumor-conditioned media (TCM). Pharmacological and metabolic analyses demonstrated an active glucose-citrate-acetyl CoA circuit in IL12-stimulated CD8+ T cells supporting an intracellular pool of acetyl CoA in an ATP-citrate lyase (ACLY)-dependent manner. Intracellular acetyl CoA levels enhanced histone acetylation, lipid synthesis, and IFNγ production, improving the metabolic and functional fitness of CD8+ T cells in tumors. Pharmacological inhibition or genetic knockdown of ACLY severely impaired IFNγ production and viability of CD8+ T cells in nutrient-restricted conditions. Furthermore, CD8+ T cells cultured in high pyruvate-containing media in vitro acquired critical metabolic features of IL12-stimulated CD8+ T cells and displayed improved antitumor potential upon adoptive transfer in murine lymphoma and melanoma models. Overall, this study delineates the metabolic configuration of CD8+ T cells required for stable effector function in tumors and presents an affordable approach to promote the efficacy of CD8+ T cells for adoptive T-cell therapy.

2022-01-01T00:00:00Z Rath, Satyajit Kanodia, Parna Kaur, Gurvinder Coshic, Poonam Chatterjee, Kabita Neeman, Teresa George, Anna Bal, Vineeta . Prabhu, Savit B https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1399 2025-12-05T12:47:35Z 2019-01-01T00:00:00Z

Title: Characterization of biological variation of peripheral blood immune cytome in an Indian cohort Authors: Rath, Satyajit; Kanodia, Parna; Kaur, Gurvinder; Coshic, Poonam; Chatterjee, Kabita; Neeman, Teresa; George, Anna; Bal, Vineeta; . Prabhu, Savit B Abstract: Immune parameters show characteristic normal baseline levels and variance in the population. We characterised the degree of inter-individual and within-individual variation over one-year time period in 33 immune cell subsets by flow cytometry in peripheral blood mononuclear cells from 43 healthy young adult volunteers. Our analysis revealed that immune subsets that showed low variability between individuals also showed low short-term fluctuations within-individuals, as well as concordance in siblings. However, when baseline levels and degree of fluctuation were considered together, individuals failed to cluster into discreet groups. Together, the data reveal complex inter-relationships between immune subsets in individuals, and provide insights into the observed heterogeneity between individuals and between multiple immune subsets.

2019-01-01T00:00:00Z Rath, Satyajit Balyan, Renu Gund, Rupali Chawla, Amanpreet Singh Khare, Satyajeet P Pradhan, Saurabh J Rane, Sanket Galande, Sanjeev Durdik, Jeannine Marie George, Anna Bal, Vineeta https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1398 2025-12-05T12:46:54Z 2019-01-01T00:00:00Z

Title: Correlation of cell-surface CD8 levels with function, phenotype and transcriptome of naive CD8 T cells Authors: Rath, Satyajit; Balyan, Renu; Gund, Rupali; Chawla, Amanpreet Singh; Khare, Satyajeet P; Pradhan, Saurabh J; Rane, Sanket; Galande, Sanjeev; Durdik, Jeannine Marie; George, Anna; Bal, Vineeta Abstract: We have previously demonstrated co-receptor level-associated functional heterogeneity in apparently homogeneous naive peripheral CD4 T cells, dependent on MHC-mediated tonic signals. Maturation pathways can differ between naive CD4 and naive CD8 cells, so we tested whether the latter showed similar co-receptor level-associated functional heterogeneity. We report that, when either polyclonal and T-cell receptor (TCR)-transgenic monoclonal peripheral naive CD8 T cells from young mice were separated into CD8hi and CD8lo subsets, CD8lo cells responded poorly, but CD8hi and CD8lo subsets of CD8 single-positive (SP) thymocytes responded similarly. CD8lo naive CD8 T cells were smaller and showed lower levels of some cell-surface molecules, but higher levels of the negative regulator CD5. In addition to the expected peripheral decline in CD8 levels on transferred naive CD8 T cells in wild-type (WT) but not in MHC class I-deficient recipient mice, short-duration naive T-cell-dendritic cell (DC) co-cultures in vitro also caused co-receptor down-modulation in CD8 T cells but not in CD4 T cells. Constitutive pZAP70/pSyk and pERK levels ex vivo were lower in CD8lo naive CD8 T cells and dual-specific phosphatase inhibition partially rescued their hypo-responsiveness. Bulk mRNA sequencing showed major differences in the transcriptional landscapes of CD8hi and CD8lo naive CD8 T cells. CD8hi naive CD8 T cells showed enrichment of genes involved in positive regulation of cell cycle and survival. Our data show that naive CD8 T cells show major differences in their signaling, transcriptional and functional landscapes associated with subtly altered CD8 levels, consistent with the possibility of peripheral cellular aging.

2019-01-01T00:00:00Z Rath, Satyajit https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1397 2025-12-05T12:45:01Z 2016-01-01T00:00:00Z

Title: Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes Authors: Rath, Satyajit Abstract: The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration.

2016-01-01T00:00:00Z