Immunotherapy and the Tumor Microenvironment in Brain Metastases from Non-Small Cell Lung Cancer: Challenges and Future Directions
Brain metastases (BMs) are a relatively common and severe complication in advanced non-small cell lung cancer (NSCLC), significantly affecting patient prognosis. Metastatic tumor cells can alter the brain tumor microenvironment (TME) to promote an immunosuppressive state, characterized by reduced in...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Current Oncology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1718-7729/32/3/171 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849342015191384064 |
|---|---|
| author | Meng Wang Jihua Yang Shuai Wang Harjot Gill Haiying Cheng |
| author_facet | Meng Wang Jihua Yang Shuai Wang Harjot Gill Haiying Cheng |
| author_sort | Meng Wang |
| collection | DOAJ |
| description | Brain metastases (BMs) are a relatively common and severe complication in advanced non-small cell lung cancer (NSCLC), significantly affecting patient prognosis. Metastatic tumor cells can alter the brain tumor microenvironment (TME) to promote an immunosuppressive state, characterized by reduced infiltration of tumor-infiltrating lymphocytes (TILs), diminished expression of programmed death-ligand 1 (PD-L1), and changes in other proinflammatory factors and immune cell populations. Microglia, the resident macrophages of the brain, play a pivotal role in modulating the central nervous system (CNS) microenvironment through interactions with metastatic cancer cells, astrocytes, and infiltrating T cells. The M2 phenotype of microglia contributes to immunosuppression in BM via the activation of signaling pathways such as STAT3 and PI3K-AKT-mTOR. Recent advances have enhanced our understanding of the immune landscape of BMs in NSCLC, particularly regarding immune evasion within the CNS. Current immunotherapeutic strategies, including immune checkpoint inhibitors, have shown promise for NSCLC patients with BM, demonstrating intracranial activity and manageable safety profiles. Future research is warranted to further explore the molecular and immune mechanisms underlying BM, aiming to develop more effective treatments. |
| format | Article |
| id | doaj-art-e077003b4aed43918a8d1bd77a0eb503 |
| institution | Kabale University |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Oncology |
| spelling | doaj-art-e077003b4aed43918a8d1bd77a0eb5032025-08-20T03:43:30ZengMDPI AGCurrent Oncology1198-00521718-77292025-03-0132317110.3390/curroncol32030171Immunotherapy and the Tumor Microenvironment in Brain Metastases from Non-Small Cell Lung Cancer: Challenges and Future DirectionsMeng Wang0Jihua Yang1Shuai Wang2Harjot Gill3Haiying Cheng4Department of Oncology (Medical Oncology), Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Oncology (Medical Oncology), Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Oncology (Medical Oncology), Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Pathology, Montefiore Medical Center, Bronx, NY 10461, USADepartment of Oncology (Medical Oncology), Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USABrain metastases (BMs) are a relatively common and severe complication in advanced non-small cell lung cancer (NSCLC), significantly affecting patient prognosis. Metastatic tumor cells can alter the brain tumor microenvironment (TME) to promote an immunosuppressive state, characterized by reduced infiltration of tumor-infiltrating lymphocytes (TILs), diminished expression of programmed death-ligand 1 (PD-L1), and changes in other proinflammatory factors and immune cell populations. Microglia, the resident macrophages of the brain, play a pivotal role in modulating the central nervous system (CNS) microenvironment through interactions with metastatic cancer cells, astrocytes, and infiltrating T cells. The M2 phenotype of microglia contributes to immunosuppression in BM via the activation of signaling pathways such as STAT3 and PI3K-AKT-mTOR. Recent advances have enhanced our understanding of the immune landscape of BMs in NSCLC, particularly regarding immune evasion within the CNS. Current immunotherapeutic strategies, including immune checkpoint inhibitors, have shown promise for NSCLC patients with BM, demonstrating intracranial activity and manageable safety profiles. Future research is warranted to further explore the molecular and immune mechanisms underlying BM, aiming to develop more effective treatments.https://www.mdpi.com/1718-7729/32/3/171brain metastasesnon-small-cell lung cancerimmune systemtumor microenvironmentimmune checkpoint inhibitors |
| spellingShingle | Meng Wang Jihua Yang Shuai Wang Harjot Gill Haiying Cheng Immunotherapy and the Tumor Microenvironment in Brain Metastases from Non-Small Cell Lung Cancer: Challenges and Future Directions Current Oncology brain metastases non-small-cell lung cancer immune system tumor microenvironment immune checkpoint inhibitors |
| title | Immunotherapy and the Tumor Microenvironment in Brain Metastases from Non-Small Cell Lung Cancer: Challenges and Future Directions |
| title_full | Immunotherapy and the Tumor Microenvironment in Brain Metastases from Non-Small Cell Lung Cancer: Challenges and Future Directions |
| title_fullStr | Immunotherapy and the Tumor Microenvironment in Brain Metastases from Non-Small Cell Lung Cancer: Challenges and Future Directions |
| title_full_unstemmed | Immunotherapy and the Tumor Microenvironment in Brain Metastases from Non-Small Cell Lung Cancer: Challenges and Future Directions |
| title_short | Immunotherapy and the Tumor Microenvironment in Brain Metastases from Non-Small Cell Lung Cancer: Challenges and Future Directions |
| title_sort | immunotherapy and the tumor microenvironment in brain metastases from non small cell lung cancer challenges and future directions |
| topic | brain metastases non-small-cell lung cancer immune system tumor microenvironment immune checkpoint inhibitors |
| url | https://www.mdpi.com/1718-7729/32/3/171 |
| work_keys_str_mv | AT mengwang immunotherapyandthetumormicroenvironmentinbrainmetastasesfromnonsmallcelllungcancerchallengesandfuturedirections AT jihuayang immunotherapyandthetumormicroenvironmentinbrainmetastasesfromnonsmallcelllungcancerchallengesandfuturedirections AT shuaiwang immunotherapyandthetumormicroenvironmentinbrainmetastasesfromnonsmallcelllungcancerchallengesandfuturedirections AT harjotgill immunotherapyandthetumormicroenvironmentinbrainmetastasesfromnonsmallcelllungcancerchallengesandfuturedirections AT haiyingcheng immunotherapyandthetumormicroenvironmentinbrainmetastasesfromnonsmallcelllungcancerchallengesandfuturedirections |