scholarly journals Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer

2014 ◽  
Vol 124 (12) ◽  
pp. 5466-5480 ◽  
Author(s):  
Evgeniy B. Eruslanov ◽  
Pratik S. Bhojnagarwala ◽  
Jon G. Quatromoni ◽  
Tom Li Stephen ◽  
Anjana Ranganathan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Human Lung ◽  
Early Stage ◽  
T Cell Responses ◽  
Human Lung Cancer ◽  
Cell Responses ◽  
Tumor Associated Neutrophils

scholarly journals Human tumor-associated monocytes/macrophages and their regulation of T cell responses in early-stage lung cancer

2019 ◽  
Vol 11 (479) ◽  
pp. eaat1500 ◽  
Author(s):  
Sunil Singhal ◽  
Jason Stadanlick ◽  
Michael J. Annunziata ◽  
Abhishek S. Rao ◽  
Pratik S. Bhojnagarwala ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Human Lung ◽  
Early Stage ◽  
T Cell Responses ◽  
Effector T Cells ◽  
Human Lung Cancer ◽  
Mouse Tumor ◽  
Cell Responses

Data from mouse tumor models suggest that tumor-associated monocyte/macrophage lineage cells (MMLCs) dampen antitumor immune responses. However, given the fundamental differences between mice and humans in tumor evolution, genetic heterogeneity, and immunity, the function of MMLCs might be different in human tumors, especially during early stages of disease. Here, we studied MMLCs in early-stage human lung tumors and found that they consist of a mixture of classical tissue monocytes and tumor-associated macrophages (TAMs). The TAMs coexpressed M1/M2 markers, as well as T cell coinhibitory and costimulatory receptors. Functionally, TAMs did not primarily suppress tumor-specific effector T cell responses, whereas tumor monocytes tended to be more T cell inhibitory. TAMs expressing relevant MHC class I/tumor peptide complexes were able to activate cognate effector T cells. Mechanistically, programmed death-ligand 1 (PD-L1) expressed on bystander TAMs, as opposed to PD-L1 expressed on tumor cells, did not inhibit interactions between tumor-specific T cells and tumor targets. TAM-derived PD-L1 exerted a regulatory role only during the interaction of TAMs presenting relevant peptides with cognate effector T cells and thus may limit excessive activation of T cells and protect TAMs from killing by these T cells. These results suggest that the function of TAMs as primarily immunosuppressive cells might not fully apply to early-stage human lung cancer and might explain why some patients with strong PD-L1 positivity fail to respond to PD-L1 therapy.

scholarly journals Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer

2017 ◽  
Vol 18 (8) ◽  
pp. 940-950 ◽  
Author(s):  
Anusha-Preethi Ganesan ◽  
James Clarke ◽  
Oliver Wood ◽  
Eva M Garrido-Martin ◽  
Serena J Chee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Human Lung ◽  
T Cell Responses ◽  
Human Lung Cancer ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses

Abstract A02: The origin and role of APC-like hybrid tumor-associated neutrophils in early-stage human lung cancer

2016 ◽  
Author(s):  
Evgeniy Eruslanov ◽  
Pratik Bhojnagarwala ◽  
Jon Quatromoni ◽  
Shaun O'Brien ◽  
Edmund Moon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Early Stage ◽  
Human Lung Cancer ◽  
Hybrid Tumor ◽  
Tumor Associated Neutrophils

Abstract 3707: Tumor-associated neutrophils with antigen-presenting features in early-stage human lung cancer

2017 ◽  
Author(s):  
Jason Stadanlick ◽  
Abhishek Rao ◽  
Michael Annunziata ◽  
Edmund Moon ◽  
Shaun O'brien ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Early Stage ◽  
Human Lung Cancer ◽  
Antigen Presenting ◽  
Tumor Associated Neutrophils

scholarly journals Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer

Cancer Cell ◽  
2016 ◽  
Vol 30 (1) ◽  
pp. 120-135 ◽  
Author(s):  
Sunil Singhal ◽  
Pratik S. Bhojnagarwala ◽  
Shaun O'Brien ◽  
Edmund K. Moon ◽  
Alfred L. Garfall ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Human Lung ◽  
Early Stage ◽  
Human Lung Cancer ◽  
Antigen Presenting Cell ◽  
Antigen Presenting ◽  
Tumor Associated Neutrophils

scholarly journals Circulating Interleukin-4 Is Associated with a Systemic T Cell Response against Tumor-Associated Antigens in Treatment-Naïve Patients with Resectable Non-Small-Cell Lung Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3496
Author(s):  
Seyer Safi ◽  
Yoshikane Yamauchi ◽  
Hans Hoffmann ◽  
Wilko Weichert ◽  
Philipp J. Jost ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
T Cell Responses ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Responses ◽  
Tumor Tissues ◽  
Cytokine Levels ◽  
Treatment Naïve

Spontaneous T cell responses to tumor-associated antigens (TAs) in the peripheral blood of patients with non-small-cell lung cancer (NSCLC) may be relevant for postoperative survival. However, the conditions underlying these T cell responses remain unclear. We quantified the levels of 27 cytokines in the peripheral blood and tumor tissues from treatment-naïve patients with NSCLC (n = 36) and analyzed associations between local and systemic cytokine profiles and both TA-specific T cell responses and clinical parameters. We defined T cell responders as patients with circulating T cells that were reactive to TAs and T cell nonresponders as patients without detectable TA-specific T cells. TA-specific T cell responses were correlated with serum cytokine levels, particularly the levels of interleukin(IL)-4 and granulocyte colony-stimulating factor (G-CSF), but poorly correlated with the cytokine levels in tumor tissues. Nonresponders showed significantly higher serum IL-4 levels than responders (p = 0.03); the predicted probability of being a responder was higher for individuals with low serum IL-4 levels. In multivariable Cox regression analyses, in addition to IL-4 (hazard ratio (HR) 2.8 (95% confidence interval (CI): 0.78–9.9); p = 0.116), the age-adjusted IL-8 level (HR 3.9 (95% CI: 1.05–14.5); p = 0.042) predicted tumor recurrence. However, this study included data for many cytokines without adjustment for multiple testing; thus, the observed differences in IL-4 or IL-8 levels might be incidental findings. Therefore, additional studies are necessary to confirm these results.

Sign in / Sign up

Export Citation Format

Share Document