Biology subjects

Ramachandran, M.

Publications and source records attributed to Ramachandran, M..

4 recordsLinked to original sources

bioRxiv2024

Cellular and molecular events organizing the assembly of tertiary lymphoid structures in glioblastoma

Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates associated with improved prognosis in numerous tumors. To date, their prognostic value in central nervous system cancers and the events underlying their formation remain unclear. Here, we find that TLS correlate with improved survival in glioblastoma patients. Furthermore, combining spatial transcriptomics of human tissues with longitudinal studies in murine glioma, we establish that the assembly of T cell-rich clusters is a prerequisite for the development of canonical TLS, and show that CD4 T cells play a central role in this process. Indeed, we provide evidence that IL7R+CCR7+ Th1 lymphocytes with lymphoid tissue-inducing potential are recruited to TLS nucleation sites, where they can initiate TLS assembly by expressing lymphotoxin {beta}. Our work defines TLS as a potential prognostic factor in glioblastoma and identifies cellular and molecular mechanisms of TLS formation. These findings have broader implications for the development of TLS-inducing therapies for cancer. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/601824v1_ufig1.gif" ALT="Figure 1"> View larger version (62K): org.highwire.dtl.DTLVardef@78be05org.highwire.dtl.DTLVardef@1037706org.highwire.dtl.DTLVardef@7b64e1org.highwire.dtl.DTLVardef@11bfd5c_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Brain tumor induce immunoregulatory dendritic cells in tumor draining lymph nodes that can be targeted by OX40

Brain tumors and metastases have a poor prognosis due to the unique characteristics of the central nervous system (CNS) and tumor immune microenvironment (TIME). CNS tumors exhibit limited infiltration and activation of dendritic cells (DCs) in tumor tissue and tumor-draining lymph nodes (TdLN), which regulate immune responses influenced by factors in the TIME. The immune response in the brain is significantly different from the rest of the body, and although DC subtypes have been identified in mice and humans with brain tumors or metastases, little is known how they affect the response to immunotherapy. We investigated the immunoregulatory function of cervical DCs (DC-c) compared to peripheral DCs (DC-p) in TdLN. Our analysis revealed that DC-c have unique phenotypes and promoted regulatory T cell expansion and poorly cytotoxic CD8 T cells compared to DC-p. Furthermore, we identified OX40 as a modulator of immunoregulatory DC-c function, and Batf3 knockout confirmed the essential role of DC-c in mounting an immune response to brain tumors. Additionally, the expression of markers associated with mature regulatory DCs (mregDC) in TdLN was associated with immune regulation in the CNS and the response to OX40. Our findings highlight that immunotherapy interventions can modulate DC-cs immunoregulatory function, offering an innovative approach for optimized immunotherapy against CNS malignancies.

immunology↗

bioRxiv2021

Agonistic CD40 antibody therapy induces tertiary lymphoid structures but impairs the response to immune checkpoint blockade in glioma

Gliomas are brain tumors characterized by immunosuppression. Immunostimulatory agonistic CD40 antibodies (CD40) are in clinical development for solid tumors but are yet to be evaluated for glioma. Here, systemic delivery of CD40 led to cytotoxic T cell dysfunction and impaired the response to immune checkpoint inhibitors in preclinical glioma models. This was associated with an accumulation of suppressive CD11b+ B cells. However, CD40 also induced tertiary lymphoid structures (TLS). In human glioma, TLS correlated with increased T cell infiltration indicating enhanced immune responses. Our work unveils the pleiotropic effects of CD40 therapy in glioma, which is of high clinical relevance.

cancer biology↗

bioRxiv2021

Essential oil composition of Callistemon citrinus (Curtis) and its protective assessment towards Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae)

Essential oil (EO) was extracted from Callistemon citrinus leaves by hydro-distillation. The extracted oil was analysed by GC and Mass Spectroscopy. Analysis report showed that the major constituent of the essential oil was eucalyptol (40.44%). The EO of C. citrinus exhibited 100% fumigation toxicity (adult mortality) against adult and 95.8% larvicidal activity against Tribolium castaneum at 160 L/L (12 hrs) and 320 L/L (48 hrs), respectively. The effective concentration of 37.05 L/L (adult) and 144.31 L/L (larva) at 24 and 48 hrs respectively. A 100% repellent activity was observed at 20 l for adult beetles and 93.3% for larvae of T. castaneum at 20 l after 24 h. Exposure to C. citrinus EO significantly reduced beetle fecundity, ovicidal activity, egg hatching, larvae survival, and emergence of adult. The effect of EO on detoxification enzymes of T. castaneum adults was examined. Results indicated that the activity of detoxification enzymes drastically varied when compared with control. This EO had toxicant effects on all stages of the life of T. castaneum. Hence it may be used as fumigant instead of the use of using synthetic chemical fumigants.

zoology↗