P2.04-19 Neoadjuvant Chemotherapy Is Associated with Immunogenic Cell Death and Increased T Cell Infiltration in Early-Stage NSCLC

AbstractThe clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.

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Copper‐Based Nanoscale Coordination Polymers Augmented Tumor Radioimmunotherapy for Immunogenic Cell Death Induction and T‐Cell Infiltration

Small ◽

10.1002/smll.202006231 ◽

2021 ◽

Vol 17 (8) ◽

pp. 2006231

Author(s):

Yuxiang Wang ◽

Yawen Ding ◽

Dan Yao ◽

Hong Dong ◽

Changwei Ji ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

Coordination Polymers ◽

Cell Infiltration ◽

Immunogenic Cell Death ◽

T Cell Infiltration ◽

Nanoscale Coordination Polymers

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Occurrence of Tertiary Lymphoid Tissue Is Associated with T-Cell Infiltration and Predicts Better Prognosis in Early-Stage Colorectal Cancers

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-13-2590 ◽

2014 ◽

Vol 20 (8) ◽

pp. 2147-2158 ◽

Cited By ~ 109

Author(s):

Giuseppe Di Caro ◽

Francesca Bergomas ◽

Fabio Grizzi ◽

Andrea Doni ◽

Paolo Bianchi ◽

...

Keyword(s):

T Cell ◽

Lymphoid Tissue ◽

Early Stage ◽

Cell Infiltration ◽

Colorectal Cancers ◽

Tertiary Lymphoid Tissue ◽

T Cell Infiltration

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Overexpression of SMARCE1 is associated with CD8+ T-cell infiltration in early stage ovarian cancer

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2014.05.031 ◽

2014 ◽

Vol 53 ◽

pp. 389-398 ◽

Cited By ~ 11

Author(s):

Antonis Giannakakis ◽

Athanasios Karapetsas ◽

Denarda Dangaj ◽

Evripidis Lanitis ◽

Janos Tanyi ◽

...

Keyword(s):

Ovarian Cancer ◽

T Cell ◽

Early Stage ◽

Cd8 T Cell ◽

Cell Infiltration ◽

T Cell Infiltration ◽

Early Stage Ovarian Cancer

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T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas

Cancer ◽

10.1002/cncr.30726 ◽

2017 ◽

Vol 123 (17) ◽

pp. 3291-3304 ◽

Cited By ~ 81

Author(s):

Seth M. Pollack ◽

Qianchuan He ◽

Jennifer H. Yearley ◽

Ryan Emerson ◽

Marissa Vignali ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

Soft Tissue ◽

Programmed Cell Death ◽

Soft Tissue Sarcomas ◽

Cell Infiltration ◽

Programmed Death Ligand 1 ◽

T Cell Infiltration ◽

Programmed Death ◽

Cell Death Protein

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The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15609 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15609-e15609 ◽

Cited By ~ 1

Author(s):

Shenying Jin ◽

Bo Xu ◽

Lixia Yu ◽

Yao Fu ◽

Hongyan Wu ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

T Cell ◽

Programmed Cell Death ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Cell Infiltration ◽

T Cell Infiltration ◽

Signet Ring ◽

Ring Cell

e15609 Background: Recent data supports a potentially significant role for immune checkpoint inhibitors in the treatment of gastric cancer. However, there are few data on the clinical implications of immunotherapy markers in gastric signet-ring cell carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), infiltration by CD3+ T cell, microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the relationship of each factor to survival in SRCC patients. Methods: SRCC samples from 89 patients were stained by immunohistochemistry to evaluate PD-L1, PD-1, CD3+ T cells, and MSI. EBV was detected by DNA in-situ hybridization. Results: All 89 patients had advanced gastric SRCC (89.9% were stage III, 10.1% were stage IV). All patients received 5-FU-based first-line chemotherapy. PD-L1 and PD-1 were expressed in 40.4% and 18.0% of the patients, respectively. There was a significant correlation between PD-L1 and PD-1 expression (r = 0.363, p < 0.001). There was loss of at least 1 of the 4 DNA mismatch repair (DNA-MMR) gene proteins in 32.6% of samples. However, there was no association between the expression of PD-L1, PD-1 or MSI status to overall survival (OS). Only 1 case out of 89 was EBV positive, with concurrent PD-L1 positivity, a high degree of CD3+ T cell infiltration and MSI. Increased CD3+ T cells numbers was associated with increased PD-1 expression (r = 0.256, p = 0.012) and MSI status (r = 0.208, p = 0.05). High CD3+ T cell infiltration was related to better OS (23.7 months, 95% CI: 19.0-38.0 vs 15.8 months, 95% CI: 13.0-22.0, p = 0.033), but was not an independent prognostic factor for survival after multivariate analysis (HR = 0.68, 95% CI: 0.42-1.10, p = 0.116). Conclusions: CD3+ T cell was more infiltrated in PD-1 positive, tumors with MSI and were associated with better OS, indicating an adaptive immune resistance may be occurring. Further research into the cancer characteristics and immunotherapy markers of the gastric SRCC immune microenvironment may highlight targets for immunotherapy.

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Characterization of evolution trajectory and immune profiling of brain metastasis in lung adenocarcinoma

npj Precision Oncology ◽

10.1038/s41698-021-00151-w ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Tao Jiang ◽

Yan Yan ◽

Kun Zhou ◽

Chunxia Su ◽

Shengxiang Ren ◽

...

Keyword(s):

Phylogenetic Analysis ◽

T Cell ◽

Brain Metastasis ◽

Lung Adenocarcinoma ◽

Early Stage ◽

Cell Infiltration ◽

Evolutionary Trajectory ◽

Primary Tumors ◽

T Cell Infiltration ◽

Immune Profiling

AbstractCharacterizing the evolutionary trajectory and immune profiling of brain metastasis (BM) may provide insights in the development of novel therapeutic strategies. Here, we performed whole-exome sequencing and multiplex immunofluorescence (MIF) of 40 samples from 12 lung adenocarcinoma (LUAD) patients with BM and compared to their paired primary tumors. We observed significantly higher intertumor heterogeneity between paired primary tumors and BMs, with only a median of 8.3% of genetic mutations identified as shared. Phylogenetic analysis revealed that BM-competent clones genetically diverged from their primary tumors at relatively early stage, suggesting that the parallel progression model is dominant. In cases with synchronous lymph node metastasis (LNM), phylogenetic analysis suggested that BM is a later event than LNM. MIF analysis found that BMs exhibited significantly lower CD8+ T cell infiltration (P = 0.048), and elevated CD4+Foxp3+ T cell infiltration (P = 0.036) and PD-1 expression (P = 0.047) in comparison to the matched primary tumors, indicating an immunosuppressive microenvironment in BMs. The current study revealed the discrepancy of mutational landscape as well as tumor immune microenvironment between BM and its primary tumor – such findings shall help us better understand the unique biological features of BM and develop innovative strategies accordingly for our patients with LUAD.

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HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior

Scientific Reports ◽

10.1038/s41598-021-93807-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maria-Fernanda Senosain ◽

Yong Zou ◽

Tatiana Novitskaya ◽

Georgii Vasiukov ◽

Aneri B. Balar ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Lung Adenocarcinoma ◽

Cancer Cells ◽

Cell Lines ◽

Early Stage ◽

Cell Number ◽

Cell Infiltration ◽

T Cell Infiltration ◽

Hla Dr

AbstractLung adenocarcinoma (ADC) is a heterogeneous group of tumors associated with different survival rates, even when detected at an early stage. Here, we aim to investigate whether CyTOF identifies cellular and molecular predictors of tumor behavior. We developed and validated a CyTOF panel of 34 antibodies in four ADC cell lines and PBMC. We tested our panel in a set of 10 ADCs, classified into long- (LPS) (n = 4) and short-predicted survival (SPS) (n = 6) based on radiomics features. We identified cellular subpopulations of epithelial cancer cells (ECC) and their microenvironment and validated our results by multiplex immunofluorescence (mIF) applied to a tissue microarray (TMA) of LPS and SPS ADCs. The antibody panel captured the phenotypical differences in ADC cell lines and PBMC. LPS ADCs had a higher proportion of immune cells. ECC clusters (ECCc) were identified and uncovered two ADC groups. ECCc with high HLA-DR expression were correlated with CD4+ and CD8+ T cells, with LPS samples being enriched for those clusters. We confirmed a positive correlation between HLA-DR expression on ECC and T cell number by mIF staining on TMA slides. Spatial analysis demonstrated shorter distances from T cells to the nearest ECC in LPS. Our results demonstrate a distinctive cellular profile of ECC and their microenvironment in ADC. We showed that HLA-DR expression in ECC is correlated with T cell infiltration, and that a set of ADCs with high abundance of HLA-DR+ ECCc and T cells is enriched in LPS samples. This suggests new insights into the role of antigen presenting tumor cells in tumorigenesis.

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