Abstract 4953: Differential expression of ICOS on circulating immune cells and tumor infiltrating lymphocytes in patient with solid tumors

For the first time in Russia the immunophenotype of tumor infiltrated lymphocytes (TIL) was investigated with the use of a method of quantitative flow cytometry. Samples from 104 patients, suffering from solid tumors (such as breast cancer, ovarian cancer, melanoma and oral cavity squamous carcinoma), were analyzed in this investigation. In the difference of cytomorphological analysis, the method of flow cytometry identified TIL in 100% of cases. In the structure of CDS+Т- lymphocytes the ratio CD4/CD8 was equal to 1,1±0,1. Serial gating strategy allowed to assess minor subpopulations of regulatory T-lymphocytes CD45+CD4+CD127+low/neg and CD45+CD8+CD28-CD11b-. Regulatory mechanisms with involvement of CD8 T-cells played the main role in the generation of immune responses at the tissue level ofpatients, suffering from solid tumors, independent of nosological form of disease.

Download Full-text

γ/δ T cell antigen receptors expressed on tumor-infiltrating lymphocytes from patients with solid tumors

European Journal of Immunology ◽

10.1002/eji.1830220310 ◽

1992 ◽

Vol 22 (3) ◽

pp. 679-687 ◽

Cited By ~ 27

Author(s):

Masanobu Nanno ◽

Hidetoshi Seki ◽

George Mathioudaki ◽

Ryuzi Suzuki ◽

Kyogo Itoh ◽

...

Keyword(s):

T Cell ◽

Solid Tumors ◽

Tumor Infiltrating Lymphocytes ◽

Antigen Receptors ◽

Cell Antigen ◽

T Cell Antigen Receptors ◽

Infiltrating Lymphocytes

Download Full-text

Immune cell composition and immunological profiles of the breast cancer microenvironment represented by histologically assessed tumor-infiltrating lymphocytes and PD-L1 expression: A systematic analysis

10.21203/rs.3.rs-687673/v1 ◽

2021 ◽

Author(s):

Toru Hanamura ◽

Shigehisa Kitano ◽

Hiroshi Kagamu ◽

Makiko Yamashita ◽

Mayako Terao ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cells ◽

Partial Correlation ◽

Immune Cell ◽

Tumor Infiltrating Lymphocytes ◽

Leukocyte Infiltration ◽

Blood Samples ◽

Tumor Tissues ◽

Cell Fractions ◽

Infiltrating Lymphocytes

Abstract Background. A better understanding of tumor immunology can facilitate the development of new treatment strategies for various malignancies. Histologically assessed tumor-infiltrating lymphocytes (hTILs) and programmed cell death 1 ligand 1 (hPD-L1) have been established as prognostic or predictive biomarkers in certain subsets of breast cancer. However, the complexity of multiple types of immune cells is not fully understood. In this study, the immune cell fractions in breast cancer tissue and blood were evaluated to analyze their association with hTILs and hPD-L1. Methods. In total, 45 tumor and 18 blood samples were collected from breast cancer patients. The total leukocyte counts, proportions of 11 types of immune cells in the samples, and PD-L1 expression in each fraction were evaluated using multicolor flow cytometry for both the tumor and blood samples. The hTILs and hPD-L1 were evaluated with hematoxylin and eosin staining and immunohistochemistry respectively. Results. The immune cell composition of the blood showed a partial correlation with that of the tumor tissue; however, no significant association was found between the blood immune cell compositions and hTIL or hPD-L1 expression. A higher hTIL was associated with increased leukocyte infiltration as well as a higher proportion of CD4+ and CD8+ T cells and lower proportion of natural killer cells and natural killer T cells. PD-L1 was highly expressed in the monocyte/macrophage (Mo/Mφ), nonclassical monocyte (CD16+ Mo), myeloid-derived suppressor cell (MDSC), dendritic cell (DC), and myeloid dendritic cell (mDC) fractions in the tumor tissues. hPD-L1 positivity was associated with increased leukocyte infiltration in the tumor tissues and PD-L1 expression in Mo/Mφ, CD16+ Mo, MDSC, DC, and mDC fractions. Conclusion. There was a partial correlation in the composition of immune cells at the tumor site and that in the peripheral blood. A high proportion of hTILs reflects not only higher immune cell infiltration but also differences in the immune responses in the tumor microenvironment. Non-B-cell antigen-presenting cell fractions such as Mo/Mφ, CD16+ Mo, MDSC, DC, and mDC fractions are involved primarily in the PD-L1 pathway in the breast cancer microenvironments.

Download Full-text

Potential therapeutic target for PD1/PDL1 blockade in microsatellite medullary carcinomas based on PDL1 expression by tumor cells and infiltration by numerous PD1+ T lymphocytes.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e14599 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e14599-e14599

Author(s):

Celine Bossard ◽

Eva Ott ◽

Delphine Dansette ◽

Adrien Ouary ◽

Anne Jarry ◽

...

Keyword(s):

Tumor Cells ◽

Immune Cells ◽

Significant Proportion ◽

Tumor Infiltrating Lymphocytes ◽

Point Of View ◽

Potential Therapeutic Target ◽

Preferential Expression ◽

Tissue Sections ◽

Clinical Point ◽

Infiltrating Lymphocytes

e14599 Background: PD1/PDL1 blockade showed therapeutic efficacy in only microsatellite (MSI) colorectal carcinomas (CRC), however, the profile of PDL1 and PD1 expression in CRC is only partially described. Methods: We thus analyzed on FFPE whole-tissue sections of 80 CRC, the expression profile of PDL1 by tumor and/or immune cells by immunohistochemistry (clone E1L3N) depending on the MSI status and the histological subtype, and correlated to the density of PD1+ and Tbet+ (able to secrete IFNg known to induce PDL1) tumor-infiltrating lymphocytes (TIL). Results: 78% of MSI CRC (32/41) overexpressed PDL1 either by tumor or immune cells versus 46% of MSS CRC (18/39) (p 0.005). This overexpression was heterogeneous within the same tumor in most of cases. Among MSI CRC, PDL1 was preferentially overexpressed in medullary carcinomas (MC, 19/21, 90%) compared with 65% (13/20) in non medullary adenocarcinomas (p 0.06). PDL1 expression by tumor cells was only observed in MSI CRC (19/41, 46% with PDL1 expression in more than 5% of tumor cells – score 1), and preferentially in MC (57% vs 5% in no medullary adenocarcinomas, with PDL1 expression in more than 50% of tumor cells – score 3, p 0.0005). Conversely, PDL1 expression by immune cells was observed in MSI CRC (23/41, 56% with PDL1 expression by more than 5 sheets of 50 positive cells) but also in MSS CRC (18/39, 43%) (p 0.5). The density of PD1+ cells was significantly correlated to the PDL1 expression, as well as the density of Tbet+ TIL. Conclusions: PDL1 expression is 1) heterogeneous in CRC, among CRC but also within the same tumor, 2) preferentially observed in MSI CRC (78%), especially in MC (90%), where PDL1 is expressed by tumor cells, 3) correlated with the density of PD1+ or Tbet+ TIL, and 4) observed in a significant proportion of MSS CRC (46%) by immune cells only. From a clinical point of view, PDL1 expression has to be determined at best in full tissue section and besides its preferential expression in MSI CRC, its significant frequency and expression profil (only by immune cells) in MSS CRC should be taken into account in the future clinical trials testing the efficacy of anti-PD1/PDL1 antibodies.

Download Full-text

Influence of preoperative chemoradiation on tumor-infiltrating lymphocytes in locally advanced rectal cancer: The STAR-01 cohort.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3611 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3611-3611

Author(s):

Francesca Negri ◽

Letizia Gnetti ◽

Lorena Bottarelli ◽

Nicoletta Campanini ◽

Maria Emanuela Negru ◽

...

Keyword(s):

Rectal Cancer ◽

T Lymphocytes ◽

Immune Cells ◽

Locally Advanced ◽

Tumor Infiltrating Lymphocytes ◽

Advanced Rectal Cancer ◽

Preoperative Chemoradiotherapy ◽

Locally Advanced Rectal Cancer ◽

Preoperative Chemoradiation ◽

Infiltrating Lymphocytes

3611 Background: Preoperative chemoradiotherapy may increase antitumor immunity through enhancing T-cell activation and tumor infiltration. These effects could possibly sensitize tumors to immunotherapies, including checkpoint inhibitors. We explored whether preoperative chemoradiation for locally advanced rectal cancer induces immunologic changes and if the post-operative biological parameters are associated with tumor regression grade (TRG sec. Ryan –AJCC Eight ed.). Methods: The multicenter STAR-01 study compared a standard preoperative chemoradiotherapy regimen (50.4 Gy in 28 daily fractions with concomitant infused fluorouracil at the dose of 225 mg/m2/d) with the same regimen plus oxaliplatin given weekly at the dose of 60 mg/m2 in patients with locally advanced rectal cancers. Paired pre- and post-operative specimens were available for 58 patients from this trial and were analyzed by immunohistochemistry. The immunoistochemical analysis was performed with a panel of immune cells and associated factors as CD3, CD20, CD4/CD8, PD1. The pattern of tumor infiltrating lymphocytes (TILs) and related infiltrating lymphocytes (RILs) was also evaluated. Response to pre-operative chemoradiotherapy was assessed according to TRG. Results: After therapy we observed a decreased CD4/CD8 ratio (p < 0.001) and reduced expression level of CD20 (p < 0.001). The expression level of CD3+ and PD-1+ cells after therapy did not change significantly. The relative increase of lymphocytes CD8+ inside CD4/CD8 ratio evaluated on post-operative samples was significantly associated with TRG 0 (p < 0.001). Conclusions: Our data suggest that chemoradiation may induce an enrichment of CD8+ T lymphocytes and this translates in better response to chemoradiation. The new frontier of best treatment could be the use of specific immune cells (T lymphocytes) to trigger the system's immune response against disease.

Download Full-text