A Fraction of CD8+ T Cells from Colorectal Liver Metastases Preferentially Repopulate Autologous Patient-Derived Xenograft Tumors as Tissue-Resident Memory T Cells

Abstract

The diversity of T cells in the human liver may reflect the composition of TILs in CRLM. Our ex vivo characterization of CRLM vs. adjacent liver tissue detected CD103+CD39+CD8+ TRM cells predominantly in CRLM, which prompted further assessments. These TRM cells responded to cognate antigens in vitro. As functional activities of autologous TILs are central to the implementation of personalized cancer treatments, we applied a patient-derived xenograft (PDX) model to monitor TILs’ capacity to control CRLM-derived tumors in vivo. We established PDX mice with CRLMs from two patients, and in vitro expansion of their respective TILs resulted in opposing CD4+ vs. CD8+ TIL ratios. These CRLMs also displayed mutated KRAS, which enabled trametinib-mediated inhibition of MEK. Regardless of the TIL subset ratio, persistent or transient control of CRLM-derived tumors of limited size by the transferred TILs was observed only after trametinib treatment. Of note, a portion of transferred TILs was observed as CD103+CD8+ TRM cells that strictly accumulated within the autologous CRLM-derived tumor rather than in the spleen or blood. Thus, the predominance of CD103+CD39+CD8+ TRM cells in CRLM relative to the adjacent liver and the propensity of CD103+CD8+ TRM cells to repopulate the autologous tumor may identify these TILs as strategic targets for therapies against advanced CRC.

The Abundance of Tumor-Infiltrating CD8+ Tissue Resident Memory T Lymphocytes Correlates with Patient Survival in Glioblastoma

“…Hence these data, together with the positive correlation between CD103 and CD69 expression and CD8 + TILs abundance, indicate that TRM cells are an important component of the CD8 + TILs in GBM patients. Moreover, the significant negative correlations between ITGAE and CD69 gene expression and molecular markers of GBM ( ITH2 , ATRX, and TP53 ) suggest a possible anti-tumoral role for CD8 + TRM T lymphocytes, similar to that found in different tumors [ 26 , 27 , 28 , 29 ].…”

Modification with Conventional Surfactants to Improve a Lipid-Based Ionic-Liquid-Associated Transcutaneous Anticancer Vaccine

“…Tumor-driven IgG is related to the growth and survival of cancer cells, and it facilitates the metastatic process and helps to developed anticancer antibodies [ 42 ]. IgG1 and IgG2a expression is beneficial, and it is directly related to the T-helper cell type (Th1 and Th2) autoimmune responses, which are associated with antitumor responses [ 21 , 43 , 44 ]. The topically applied IL/NP(+) formulation induced the highest levels of total IgG, IgG1, and IgG2a expression, outperforming subcutaneous IL/NP(+) and transdermal IL/NP(−) in terms of the immune response.…”

“…Cytotoxic (CD8+) T-cells in tumor tissues were quantified by staining nuclei with the fluorescent dye DAPI [ 43 ]. The number of CD8+ T-cells in in the TME was visualized and quantified using a fluorescence microscopic analyzer (BZ-900; Keyence, Osaka, Japan) and ImageJ software [ 4 , 44 ]. The TME observation is briefly described in Supplementary materials S-1.7 .…”

A type I interferon footprint in pre-operative biopsies is an independent biomarker that in combination with CD8 + T cell quantification can improve the prediction of response to neoadjuvant treatment of rectal adenocarcinoma

“…Slides were kept at room temperature overnight and then incubated at 60°C for 1 h. Deparaffinization prior to staining was performed by submerging the slides for 5 min in xylene (twice) and in ethanol [99.5% (twice), 95%, 70%] and distilled water. Deparaffinized slides were stained as previously described 25 . Antibodies and TSA reagents used for the mIF are specified in Table S1.…”

“…The corresponding areas were then localized on immunofluorescence-stained sections (Figure S2a). Immunofluorescence-stained slides were scanned with TissueFAXS (TissueGnostics; Vienna, Austria) and analyzed with the StrataQuest Software (v. 7.0.1.189; TissueGnostics) as in 25 . In addition, the intensity of the antibody fluorescently labeled markers was defined and used to identify the different cell types.…”