Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples
Abstract Small cell lung carcinomas (SCLC) are aggressive tumors with high propensity to metastasize. Recent NCCN guidelines have incorporated immunotherapy in extensive stage SCLC. Limited benefit in few patients compounded by side effects of unwonted immune-checkpoint-inhibitor (ICPI) usage necess...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-30841-3 |
| _version_ | 1797864869943312384 |
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| author | Rimlee Dutta Amber Rathor Hanuman Prasad Sharma Hem Chandra Pandey Prabhat Singh Malik Anant Mohan Aruna Nambirajan Rajeev Kumar Deepali Jain |
| author_facet | Rimlee Dutta Amber Rathor Hanuman Prasad Sharma Hem Chandra Pandey Prabhat Singh Malik Anant Mohan Aruna Nambirajan Rajeev Kumar Deepali Jain |
| author_sort | Rimlee Dutta |
| collection | DOAJ |
| description | Abstract Small cell lung carcinomas (SCLC) are aggressive tumors with high propensity to metastasize. Recent NCCN guidelines have incorporated immunotherapy in extensive stage SCLC. Limited benefit in few patients compounded by side effects of unwonted immune-checkpoint-inhibitor (ICPI) usage necessitates identification of potential biomarkers predicting response to ICPIs. Attempting this, we analysed expression of various immunoregulatory molecules in tissue biopsies and paired blood samples of SCLC patients. In 40 cases, immunohistochemistry for expression of immune inhibitory receptors CTLA-4, PD-L1 and IDO1 was performed. Matched blood samples were quantified for IFN-γ, IL-2, TNF-α and sCTLA-4 levels using immunoassay and additionally for IDO1 activity (Kynurenine/Tryptophan ratio) using LC–MS. Immunopositivity for PD-L1, IDO1 and CTLA-4 was identified in 9.3%, 6.2% and 71.8% cases, respectively. Concentration of serum IFN-γ (p-value < 0.001), TNF-α (p-value = 0.025) and s-CTLA4 (p-value = 0.08) were higher in SCLC patients while IL-2 was lower (p-value = 0.003) as compared to healthy controls. IDO1 activity was significantly elevated in SCLC cohort (p-value = 0.007). We proffer that SCLC patients show immune suppressive milieu in their peripheral circulation. Analysis of CTLA4 immunohistochemical expression along with s-CTLA4 levels appears prospective as biomarkers for predicting responsiveness to ICPIs. Additionally, evaluation of IDO1 appears cogent both as prognostic marker and potential therapeutic target as well. |
| first_indexed | 2024-04-09T22:58:57Z |
| format | Article |
| id | doaj.art-f6019a1d55154868968f8e843eaae1eb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T22:58:57Z |
| publishDate | 2023-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f6019a1d55154868968f8e843eaae1eb2023-03-22T11:07:17ZengNature PortfolioScientific Reports2045-23222023-03-0113111010.1038/s41598-023-30841-3Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samplesRimlee Dutta0Amber Rathor1Hanuman Prasad Sharma2Hem Chandra Pandey3Prabhat Singh Malik4Anant Mohan5Aruna Nambirajan6Rajeev Kumar7Deepali Jain8Department of Pathology, All India Institute of Medical SciencesDepartment of Pathology, All India Institute of Medical SciencesBioanalytics Facility, Centralized Core Research Facility, All India Institute of Medical SciencesDepartment of Transfusion Medicine, All India Institute of Medical SciencesDepartment of Medical Oncology, Dr B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical SciencesDepartment of Pulmonary Medicine, All India Institute of Medical SciencesDepartment of Pathology, All India Institute of Medical SciencesDelhi Cancer Registry, Dr B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical SciencesDepartment of Pathology, All India Institute of Medical SciencesAbstract Small cell lung carcinomas (SCLC) are aggressive tumors with high propensity to metastasize. Recent NCCN guidelines have incorporated immunotherapy in extensive stage SCLC. Limited benefit in few patients compounded by side effects of unwonted immune-checkpoint-inhibitor (ICPI) usage necessitates identification of potential biomarkers predicting response to ICPIs. Attempting this, we analysed expression of various immunoregulatory molecules in tissue biopsies and paired blood samples of SCLC patients. In 40 cases, immunohistochemistry for expression of immune inhibitory receptors CTLA-4, PD-L1 and IDO1 was performed. Matched blood samples were quantified for IFN-γ, IL-2, TNF-α and sCTLA-4 levels using immunoassay and additionally for IDO1 activity (Kynurenine/Tryptophan ratio) using LC–MS. Immunopositivity for PD-L1, IDO1 and CTLA-4 was identified in 9.3%, 6.2% and 71.8% cases, respectively. Concentration of serum IFN-γ (p-value < 0.001), TNF-α (p-value = 0.025) and s-CTLA4 (p-value = 0.08) were higher in SCLC patients while IL-2 was lower (p-value = 0.003) as compared to healthy controls. IDO1 activity was significantly elevated in SCLC cohort (p-value = 0.007). We proffer that SCLC patients show immune suppressive milieu in their peripheral circulation. Analysis of CTLA4 immunohistochemical expression along with s-CTLA4 levels appears prospective as biomarkers for predicting responsiveness to ICPIs. Additionally, evaluation of IDO1 appears cogent both as prognostic marker and potential therapeutic target as well.https://doi.org/10.1038/s41598-023-30841-3 |
| spellingShingle | Rimlee Dutta Amber Rathor Hanuman Prasad Sharma Hem Chandra Pandey Prabhat Singh Malik Anant Mohan Aruna Nambirajan Rajeev Kumar Deepali Jain Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples Scientific Reports |
| title | Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples |
| title_full | Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples |
| title_fullStr | Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples |
| title_full_unstemmed | Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples |
| title_short | Mapping the immune landscape in small cell lung cancer by analysing expression of immuno-modulators in tissue biopsies and paired blood samples |
| title_sort | mapping the immune landscape in small cell lung cancer by analysing expression of immuno modulators in tissue biopsies and paired blood samples |
| url | https://doi.org/10.1038/s41598-023-30841-3 |
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