02765nas a2200229   4500008004100000022001400041245012900055210006900184260000800253300000800261490000800269520187300277653005302150653002102203653003202224653003602256653003402292653003802326100001902364700002102383856013102404       2024                        eng d  a1617-461500aDifferential cellular communication in tumor immune microenvironment during early and advanced stages of lung adenocarcinoma0 aDifferential cellular communication in tumor immune microenviron  cDEC  a1000 v2993 a<p>
	Heterogeneous behavior of each cell type and their cross-talks in tumor immune microenvironment (TIME) refers to tumor immunological heterogeneity that emerges during tumor progression and represents formidable challenges for effective anti-tumor immune response and promotes drug resistance. To comprehensively elucidate the heterogeneous behavior of individual cell types and their interactions across different stages of tumor development at system level, a computational framework was devised that integrates cell specific data from single-cell RNASeq into networks illustrating interactions among signaling and metabolic response genes within and between cells in TIME. This study identified stage specific novel markers which remodel the cross-talks, thereby facilitating immune stimulation. Particularly, multicellular knockout of metabolic gene APOE (Apolipoprotein E in mast cell, myeloid cell and fibroblast) combined with signaling gene CAV1 (Caveolin1 in endothelial and epithelial cells) resulted in the activation of T-cell mediated signaling pathways. Additionally, this knockout also initiated intervention of cytotoxic gene regulations during tumor immune cell interactions at the early stage of Lung Adenocarcinoma (LUAD). Furthermore, a unique interaction motif from multiple cells emerged significant in regulating the overall immune response at the advanced stage of LUAD. Most significantly, FCER1G (Fc Fragment of IgE Receptor Ig) was identified as the common regulator in activating the anti-tumor immune response at both stages. Predicted markers exhibited significant association with patient overall survival in patient specific dataset. This study uncovers the significance of signaling and metabolic interplay within TIME and discovers important targets to enhance anti-tumor immune response at each stage of tumor development.</p>
10aEarly and advanced stages of Lung Adenocarcinoma10aImmunomodulation10aMulticellular communication10aSignaling-metabolic cross-talks10aTumor immune microenvironment10aTumor immunological heterogeneity1 aShukla, Mudita1 aSarkar, Ram, Rup  uhttps://library.ncl.res.in/content/differential-cellular-communication-tumor-immune-microenvironment-during-early-and-advanced