The tumor stroma is an essential component of the tumor microenvironment (TME) and has critical roles in promoting resistance to immunotherapies. Most anticancer therapies target cancer cells specifically, however, it is important to also study signaling contributions from the TME. The recruitment of immune cells following intratumoral administration of Stimulation of Interferon Genes (STING) agonists in the TME is a critical event in the cGAS-STING-driven antitumor immune response, a pathway with great relevance in the context of cancer immunotherapy. Towards this, the infiltration of immune cells rely on functional vasculature to infiltrate into the tumor tissue. We have previously demonstrated that LKB1 mutation is associated with suppression of tumor cell STING levels due to mitochondrial dysfunction and reduced production of T-cell chemoattractants such as CXCL10 in KRAS-driven non-small cell lung cancer (NSCLC). Consistently, immunohistochemical staining of patient samples showed poor infiltration of CD3, CD4, and CD8 T cells into LKB1 negative versus LKB1 intact cancer epithelium, and instead, retention of T-cells in stroma.

Tumor-Stroma Interactions Promote cGAS-STING Driven Inflammation in Lung Tumor Microenvironment / Campisi, M.; Sundararaman, S.; Kitajima, S.; Canadas, I.; Chiono, V.; Kamm, R.; Barbie, D.. - In: JOURNAL OF THORACIC ONCOLOGY. - ISSN 1556-0864. - ELETTRONICO. - 14:10(2019), pp. 717-717. [https://doi.org/10.1016/j.jtho.2019.08.1528]

Tumor-Stroma Interactions Promote cGAS-STING Driven Inflammation in Lung Tumor Microenvironment

M. Campisi;V. Chiono;
2019

Abstract

The tumor stroma is an essential component of the tumor microenvironment (TME) and has critical roles in promoting resistance to immunotherapies. Most anticancer therapies target cancer cells specifically, however, it is important to also study signaling contributions from the TME. The recruitment of immune cells following intratumoral administration of Stimulation of Interferon Genes (STING) agonists in the TME is a critical event in the cGAS-STING-driven antitumor immune response, a pathway with great relevance in the context of cancer immunotherapy. Towards this, the infiltration of immune cells rely on functional vasculature to infiltrate into the tumor tissue. We have previously demonstrated that LKB1 mutation is associated with suppression of tumor cell STING levels due to mitochondrial dysfunction and reduced production of T-cell chemoattractants such as CXCL10 in KRAS-driven non-small cell lung cancer (NSCLC). Consistently, immunohistochemical staining of patient samples showed poor infiltration of CD3, CD4, and CD8 T cells into LKB1 negative versus LKB1 intact cancer epithelium, and instead, retention of T-cells in stroma.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11583/2852595