Dataset Information

B cell-dependent subtypes and treatment-based immune correlates to survival in stage 3 and 4 lung adenocarcinomas.

ABSTRACT: Lung cancer is the leading cause of cancer-related deaths worldwide. Surgery and chemoradiation 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.

SUBMITTER: Raju Paul S

PROVIDER: S-EPMC10068771 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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B cell-dependent subtypes and treatment-based immune correlates to survival in stage 3 and 4 lung adenocarcinomas.

Raju Paul Susan S Valiev Ivan I Korek Skylar E SE Zyrin Vladimir V Shamsutdinova Diana D Gancharova Olga O Zaitsev Alexander A Nuzhdina Ekaterina E Davies Diane L DL Dagogo-Jack Ibiayi I Frenkel Felix F Brown Jessica H JH Hess Joshua M JM Viet Sarah S Petersen Jason L JL Wright Cameron D CD Ott Harald C HC Auchincloss Hugh G HG Muniappan Ashok A Shioda Toshihiro T Lanuti Michael M Davis Christel M CM Ehli Erik A EA Hung Yin P YP Mino-Kenudson Mari M Tsiper Maria M Sluder Ann E AE Reeves Patrick M PM Kotlov Nikita N Bagaev Alexander A Ataullakhanov Ravshan R Poznansky Mark C MC

FASEB bioAdvances 20230216 4

Lung cancer is the leading cause of cancer-related deaths worldwide. Surgery and chemoradiation 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 th ...[more]

PMID: 37020749

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Project description:BackgroundSmall cell lung cancer (SCLC) represents approximately 15% of lung cancers, and approximately 70% are diagnosed as extensive-stage SCLC (ES-SCLC). Although ES-SCLC is highly responsive to chemotherapy, patients typically progress rapidly, and there is an urgent need for new therapies. Immune checkpoint inhibitors (ICIs) have recently been investigated in SCLC, and this review provides guidance on the use of these agents in ES-SCLC based on phase III evidence.MethodsPublished and presented literature on phase III data addressing use of ICIs in ES-SCLC was identified using the key search terms "small cell lung cancer" AND "checkpoint inhibitors" (OR respective aliases). Directed searches of eligible studies were periodically performed to ensure capture of the most recent data.ResultsSix phase III trials were identified, with four assessing the benefits of ICIs plus chemotherapy first-line, one evaluating ICIs as first-line therapy maintenance, and one assessing ICI monotherapy after progression on platinum-based chemotherapy. The addition of ipilimumab or tremelimumab to first-line treatment or as first-line maintenance did not improve survival. Two out of three studies combining PD-1/PD-L1 inhibitors with first-line platinum-based chemotherapy demonstrated significant long-lasting survival benefits and improved quality of life with no unexpected safety concerns. PD-1/PD-L1 inhibitors as first-line maintenance or in later lines of therapy did not improve survival. Biomarker research is ongoing as well as research into the role of ICIs in combination with radiation therapy in limited-stage SCLC.ConclusionThe addition of atezolizumab or durvalumab to first-line platinum-based chemotherapy for ES-SCLC prolongs survival and improves quality of life.Implications for practicePlatinum-based chemotherapy has been standard of care for extensive-stage small cell lung cancer (ES-SCLC) for more than a decade. Six recent phase III trials investigating immune checkpoint inhibitors (ICIs) have clarified the role of these agents in this setting. Although ICIs were assessed first-line, as first-line maintenance, and in later lines of therapy, the additions of atezolizumab or durvalumab to first-line platinum-based chemotherapy were the only interventions that significantly improved overall survival and increased quality of life. These combinations should therefore be considered standard therapy for first-line ES-SCLC. Biomarker research and investigations into the role of ICIs for limited-stage disease are ongoing.

Dataset Information

B cell-dependent subtypes and treatment-based immune correlates to survival in stage 3 and 4 lung adenocarcinomas.

Publications

B cell-dependent subtypes and treatment-based immune correlates to survival in stage 3 and 4 lung adenocarcinomas.

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