Protein Expression of immune checkpoints STING and MHCII in small cell lung cancer

Dora, David and Rivard, Christopher and Yu, Hui and Pickard, Shivaun Lueke and Laszlo, Viktoria and Harko, Tunde and Megyesfalvi, Zsolt and Gerdan, Csongor and Dinya, Elek and Hoetzenecker, Konrad and Hirsch, Fred R. and Lohinai, Zoltan and Dome, Balazs (2023) Protein Expression of immune checkpoints STING and MHCII in small cell lung cancer. Cancer Immunology, Immunotherapy, 72 (3). pp. 561-578. ISSN 0340-7004

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Abstract

Background SCLC is an aggressive malignancy where immunotherapies show limited efcacy. We aimed to characterize the SCLC microenvironment according to the expression patterns of SCLC subtype markers and novel immune checkpoints to identify therapeutic vulnerabilities. Methods We included SCLC tissue samples from 219 surgically resected, limited-stage patients in this cross-sectional study. We performed immunohistochemistry for STING and MHCII, as well as for the novel subtype markers (ASCL1, NEUROD1, POU2F3, YAP1). Moreover, we assessed CD45+, CD8+and CD68+immune cell infltration. Results 36% of SCLC tumors showed signifcant stromal or intraepithelial CD45+immune cell infltration. These patients exhibited signifcantly increased overall survival (OS) (vs. patients with immune-deserted tumors). High CD8 expression was associated with increased median OS. We found STING expression on cancer-associated fbroblasts in the stroma and on T-cells and macrophages in both tumorous and stromal compartments. STING expression positively correlated with immune cell infltration. Increased STING-positivity in tumor nests was an independent favorable prognosticator for OS. ASCL1 was the most frequently expressed subtype-specifc protein. Concomitant expression of three or four subtype-defning markers was seen in 13.8% of the included samples, whereas 24.1% of the cases were classifed as quadruple negative tumors. YAP1 expression was associated with increased immune infltrates. Tumor cell MHCII expression positively correlated with immune cell infltration and with STING- and YAP1 expressions. Conclusions STING and MHCII are expressed in SCLC. The majority of immune-infltrated SCLCs exhibit increased STING expression. Immune infltration and STING expression are prognostic in limited-stage SCLC, making STING a potential therapeutic target

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