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Gene Therapy for Lung Cancer
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
Choon Taek Lee, David P. Carbone
Genetic modification of immune effectors to increase cytotoxicity has also been explored. Tumor-infiltrating lymphocytes (TIL) are lymphocytes within a tumor mass that have homed to the tumor. Rosenberg et al. (47,48) have utilized TNF gene-transduced autologous TIL in advanced cancer patients and demonstrated enhanced antitumor effects with less toxicity than systemic administration. Transduction with chimeric T-cell receptor and antibody has the potential to improve targeting and killing by these effectors as well (48).
Therapy with lnterleukin-2 and Tumor-Derived Activated Lymphocytes
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
The heterogeneity of human cancer is a major impediment to successful cancer therapy (1). Attempts to manage heterogeneity therapeutically using both conventional (2) and biological (3) methodologies have met with limited success. Heterogeneity is based on cell cycle, cell differentiation, tissue or organ distribution, and results in differential cell surface antigen expression (4–8). This variability supports the use of a population of cytolytic effector cells called lymphokine-activated killer (LAK) cells (9–12). Although some reactivity against normal cells has been reported (12,13), the bulk of cytolytic activity is seen against autologous or allogeneic tumor cells. More recently, methods have become available to generate tumor derived cytotoxic T lymphocytes (TDAC - tumor-derived activated cells). These cells, also called TIL (tumor infiltrating lymphocytes) because of their specificity, are less likely to destroy normal host tissue and show more specificity for each patient’s cancer (14–16).
Polyphenols and Cancer Immunology
Published in Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri, Plants That Fight Cancer, 2019
Tumor-infiltrating lymphocytes (TILs) are a heterogeneous population of cells which infiltrate the structure of solid tumors. TILs include granulocytes, macrophages, and MDSCs originating from myeloid lineage as well as subsets of T, B, and NK lymphocytes. It is believed that the myeloid cells which infiltrate tumors are largely responsible for their progression, while T-cells, especially the CD8+ subset, are associated with tumor regression and a better prognosis for the patient (Yu and Fu 2006, Peddareddigari et al. 2010).
Immune checkpoint inhibitors: maximizing benefit whilst minimizing toxicity
Published in Expert Review of Anticancer Therapy, 2023
Catherine C. Fahey, Thomas J. Gracie, Douglas B. Johnson
The role of T cells in the tumor microenvironment and their effect on immunotherapy response has been studied extensively. Although the presence of tumor-infiltrating lymphocytes (TILs) is a good prognostic marker in many solid tumors, their presence is also indicative of failure of the immune system to eliminate cancer cells [80]. As discussed above, continuous antigen exposure leads to the expression of LAG-3, PD-1, and other inhibitor receptors, known as T cell exhaustion [40,80]. Exhausted T cells show a gradual loss of effector functions, reduced production of effector cytokines, and altered gene expression [80]. An in-depth study of these exhausted T cells has shown that there are distinct subpopulations of T cells among TILs, including both progenitor exhausted and terminally exhausted TILs [81,82]. In an analysis of melanoma samples, increased levels of progenitor exhausted T cells correlated with improved PFS [81]. This increase was specific to the progenitor T cells, as PFS did not correlate with higher total levels of CD8+ cells. This work supports the role of specific TIL analysis as a biomarker of responsiveness.
Identification of key genes and miRNA-mRNA regulatory networks associated with bone marrow immune microenvironment regulations in multiple myeloma by integrative bioinformatics analysis
Published in Hematology, 2022
Niluopaer Tuerxun, Jie Wang, Yu-ting Qin, Fang Zhao, Huan Wang, Jian-hua Qu, Md. Nazim Uddin, Jian-ping Hao
The level of tumor-infiltrating lymphocytes (TILs) is an independent predictor of survival in cancer [45]. We investigated the correlations between the expression levels of two hub genes (CDKN2A and TP53) and the levels of immune signatures in the TME of MM. Interestingly, we found that the expression level of CDKN2A is negatively correlated with immune scores (R = −0.27, P < 2.2e-16) and microenvironment scores (R = −0.31, P < 2.2e-16) (Figure 4A), but TP53 is not correlated with immune scores and tumor microenvironment scores. Furthermore, the expression level of CDKN2A is positively correlated with CD4+ Regulatory T cells, T cell exhaustion, MHC Class I, and immune checkpoint genes (Figure 4B) and negatively correlated with the macrophages, Neutrophils, and TH2 cells in the TME of MM (Figure 4B). It was indicated that the CD4 T cells are responsible for controlling autoimmune phenomena in MM [46]. T cell exhaustion in multiple myeloma is associated with the relapse of the disease [47]. Immune checkpoint pathways are associated with impeding antitumor immune responses and contributing to malignancy's persistence and/or relapse [48]. Macrophages and neutrophils are now considered critical regulatory components of the hematopoietic niche [49]. Altogether, these results indicate that the expression level of CDKN2A is associated with the immunosuppressive TME in MM.
IRE1α overexpression in malignant cells limits tumor progression by inducing an anti-cancer immune response
Published in OncoImmunology, 2022
Adriana Martinez-Turtos, Rachel Paul, Manuel Grima-Reyes, Hussein Issaoui, Adrien Krug, Rana Mhaidly, Jozef P. Bossowski, Johanna Chiche, Sandrine Marchetti, Els Verhoeyen, Eric Chevet, Jean-Ehrland Ricci
Intra-tumoral infiltration of immune cell populations was calculated as a percentage of the whole tumor. Tumor-infiltrating lymphocytes (TILs) were defined as followed: CD3+ TILs (CD3+/CD45+), CD8+ TILs (CD8+/CD3+), and CD4+ TILs (CD4+/CD3+). Infiltrating NK cells were defined as CD49b+/CD3−/CD45+. Tumor assoiated macrophages (TAMs) were defined as CD86+/CD11c+/CD11b+/F4/80+/CD45+ in CTR and Low PROT tumors, while resident TMAs were defined as CD64+/Mertk+/CD45+ cells in mock and overexpressed tumors. Mock and IRE1α-overexpressing tumor cells were defined as GFP+/CD45− while CRISPR/Cas control and IRE1α knockout tumor cells were defined as CD45− cells.