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B cell-dependent subtypes and treatment-based immune correlates to survival in stage 3 and 4 lung adenocarcinomasстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Paul Susan Raju, Valiev Ivan, Korek Skylar E., Zyrin Vladimir, Shamsutdinova Diana, Gancharova Olga, Zaitsev Alexander, Nuzhdina Ekaterina, Davies Diane L., Dagogo-Jack Ibiayi, Frenkel Felix, Brown Jessica H., Hess Joshua M., Viet Sarah, Petersen Jason L., Wright Cameron D., Ott Harald C., Auchincloss Hugh G., Muniappan Ashok, Shioda Toshihiro, Lanuti Michael, Davis Christel M., Ehli Erik A., Hung Yin P., Mino-Kenudson Mari, Tsiper Maria, Sluder Ann E., Reeves Patrick M., Kotlov Nikita, Bagaev Alexander, Ataullakhanov Ravshan, Poznansky Mark C.
- Журнал: FASEB Journal
- Год издания: 2023
- Издательство: Federation of American Societies for Experimental Biology
- Местоположение издательства: United States
- DOI: 10.1096/fba.2023-00009
- Аннотация: Lung cancer is the leading cause of cancer-related deaths worldwide. Surgery and chemo-radiation are the standard of care in early stages of non-small cell lung cancer (NSCLC), while immunotherapy is the standard of care in late-stage NSCLC. The immune composition of the tumor microenvironment (TME) is recognized as an indicator for responsiveness to immunotherapy, although much remains unknown about its role in responsiveness to surgery or chemoradiation. In this pilot study, we characterized the NSCLC TME using mass cytometry (CyTOF) and bulk RNA sequencing (RNA-Seq) with deconvolution of RNA-Seq being performed by Kassandra, a recently published deconvolution tool. Stratification of patients based on the intratumoral abundance of B-cells identified that the B-cell rich patient group had increased expression of CXCL13 and greater abundance of PD1+ CD8 T cells. The presence of B cells and PD1+ CD8 T cells correlated positively with the presence of intratumoral tertiary lymphoid structures (TLS). We then assessed the predictive and prognostic utility of these cell types and TLS within publicly available stage 3 and 4 lung adenocarcinoma (LUAD) RNA-Seq datasets. As previously described by others, pre-treatment expression of intratumoral 12-chemokine TLS gene signature is associated with progression free survival (PFS) in patients who receive treatment with immune checkpoint inhibitors (ICI). Notably and unexpectedly pre-treatment percentages of intratumoral B cells are associated with PFS in patients who receive surgery, chemotherapy or radiation. Further studies to confirm these findings would allow for more effective patient selection for both ICI and non-ICI treatments.
- Добавил в систему: Ганчарова Ольга Сергеевна