CD8+ T Cells Form the Predominant Subset of NKG2A+ Cells in Human Lung Cancer

This study was designed to characterize the microbiomes of the lung tissues of lung cancer patients. RNA-sequencing was performed on lung tumor samples from 49 patients with lung cancer. Metatranscriptomics data were analyzed using SAMSA2 and Kraken2 software. 16S rRNA sequencing was also performed. The heterogeneous cellular landscape and immune repertoires of the lung samples were examined using xCell and TRUST4, respectively. We found that nine bacteria were significantly enriched in the lung tissues of cancer patients, and associated with reduced overall survival (OS). We also found that subjects with mutations in the epidermal growth factor receptor gene were less likely to experience the presence of Pseudomonas. aeruginosa. We found that the presence of CD8+ T-cells, CD4+ naive T-cells, dendritic cells, and CD4+ central memory T cells were associated with a good prognosis, while the presence of pro B-cells was associated with a poor prognosis. Furthermore, high clone numbers were associated with a high ImmuneScore for all immune receptor repertoires. Clone numbers and diversity were significantly higher in unpresented subjects compared to presented subjects. Our results provide insight into the microbiota of human lung cancer, and how its composition is linked to the tumor immune microenvironment, immune receptor repertoires, and OS.

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Recognition of a Purified Mr-40,000 Organ-Specific Immunogen of Human Lung Cancer by Class II-Restricted T-Cells2

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/79.4.653 ◽

1987 ◽

Keyword(s):

Lung Cancer ◽

T Cells ◽

Human Lung ◽

Class Ii ◽

Human Lung Cancer ◽

Organ Specific

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Faculty Opinions recommendation of Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736030378.793575846 ◽

2020 ◽

Author(s):

Gabrielle Belz

Keyword(s):

Lung Cancer ◽

T Cells ◽

Single Cell ◽

Human Lung ◽

Memory T Cells ◽

Transcriptomic Analysis ◽

Human Lung Cancer ◽

Resident Memory T Cells

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Activation of T Cells upon Treatment with Bispecific Antibodies Correlates with the Expression of Co-Inhibitory Receptors on Tumor-Infiltrating Lymphocytes in Human Lung Cancer

Annals of Oncology ◽

10.1093/annonc/mdu466.2 ◽

2014 ◽

Vol 25 ◽

pp. vi1

Author(s):

D. Thommen ◽

J. Schreiner ◽

P. Herzig ◽

P. Mueller ◽

V. Karanikas ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

Human Lung ◽

Tumor Infiltrating Lymphocytes ◽

Bispecific Antibodies ◽

Human Lung Cancer ◽

Inhibitory Receptors ◽

Infiltrating Lymphocytes

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The Characteristics of Naive-like T Cells in Tumor-infiltrating Lymphocytes From Human Lung Cancer

Journal of Immunotherapy ◽

10.1097/cji.0000000000000147 ◽

2017 ◽

Vol 40 (1) ◽

pp. 1-10 ◽

Cited By ~ 11

Author(s):

Si Yuan Sheng ◽

Yong Gu ◽

Chuan Gang Lu ◽

Ying Ying Tang ◽

Jian Yong Zou ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

Human Lung ◽

Tumor Infiltrating Lymphocytes ◽

Human Lung Cancer ◽

Infiltrating Lymphocytes

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Dual but not single PD-1 or TIM-3 blockade enhances oncolytic virotherapy in refractory lung cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2019-000294 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000294

Author(s):

Fan Sun ◽

Zong Sheng Guo ◽

Alyssa D Gregory ◽

Steven D Shapiro ◽

Gutian Xiao ◽

...

Keyword(s):

Lung Cancer ◽

T Cells ◽

T Cell ◽

Tumor Cells ◽

Immune Cells ◽

Human Lung ◽

Human Lung Cancer ◽

Cancer Model ◽

Triple Combination Therapy ◽

Mutual Induction

BackgroundProgrammed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy fails in the majority of patients with cancer. Oncolytic viruses represent a new class of therapeutic agents, yet the therapeutic efficacy is still disappointing. Moreover, intratumoral injection of viruses is the main approach and preclinical studies mainly employ syngeneic or xenograft models.MethodsUse an endogenous mouse lung cancer model that faithfully recapitulates human lung cancer, and various in vivo, ex vivo and in vitro assays, to investigate the efficacy, mechanism of action and resistance of systemically administered oncolytic vaccinia virus (oVV), immunotherapy and their combination, to find an effective therapy for refractory lung cancer.ResultsResembling human lung cancers, the majority of which are largely resistant to PD-1/PD-L1 blockade and with decreased PD-L1 expression and T-cell activation by our analysis, urethane-induced endogenous lung tumors in mice show reduced PD-L1 expression, low tumor-infiltrating lymphocytes and innate resistance to PD-1/PD-L1 blockade. Intravenous administration of oVV has efficacy and synergizes with simultaneous but not single blockade of PD-1 and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in this cancer model. Besides direct tumor cell killing, oVV induces T-cell lung recruitment, tumor infiltration, along with expression of PD-1 and TIM-3 on T cells and PD-1 and TIM-3 ligands on tumor cells and tumor-associated immune cells. Blockade of PD-1 or TIM-3 also causes their mutual induction on T cells.ConclusionsWhile systemic administration of oVV shows efficacy in lung cancer by killing tumor cells directly and recruiting and activating T cells for indirect tumor killing, its induction of PD-1 and TIM-3 on T cells and PD-1 and TIM-3 ligands on tumors and tumor-associated immune cells as well as mutual induction of PD-1 or TIM-3 on T cells by their blockade restricts the efficacy of oVV or its combination with single PD-1 or TIM-3 blockade. The triple combination therapy is more effective for refractory lung cancer, and possibly other cold cancers as well.

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

Science Translational Medicine ◽

10.1126/scitranslmed.aat1500 ◽

2019 ◽

Vol 11 (479) ◽

pp. eaat1500 ◽

Cited By ~ 36

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.

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