Lymphocyte Networks are Dynamic Cellular Communities in the Immunoregulatory Landscape of Lung Adenocarcinoma

Unveiling the impact of tertiary lymphoid structures on immunotherapeutic responses of clear cell renal cell carcinoma

“…Evidences suggest that E-TLS may be initiated from T cell factor 1 (TCF-1) -expressing stem-like T cells, which may interact with CD4 + CXCL13 + T helper cells and consequently attract B cells. 42,43 However, E-TLS lack sufficient antigen presentation and therefore specific antitumor response are obstructed. While mature TLS (PFL-TLS and SFL-TLS) take the antitumor immunity a significant step further as characterized by the FDC network.…”

“…Since the intratumoral TLS that predict the better prognosis are predominantly mature TLS, investigating if TLS maturation could be the confounding reason for the difference in prognostic associations in ccRCC rather than the localization constitutes a possible goal for future research. Evidences suggest that E‐TLS may be initiated from T cell factor 1 (TCF‐1) ‐expressing stem‐like T cells, which may interact with CD4 + CXCL13 + T helper cells and consequently attract B cells 42,43 . However, E‐TLS lack sufficient antigen presentation and therefore specific antitumor response are obstructed.…”

Coordinated Immune Cell Networks in the Bone Marrow Microenvironment Define the Graft versus Leukemia Response with Adoptive Cellular Therapy

“…Highly coordinated immune cell networks with enrichment of activated or cytotoxic T cells have recently been identified as key features associated with response to immunotherapy across a variety of cancer types, largely focused on solid tumor responses to immune checkpoint blockade (ICB). 88,[90][91][92][93] In these settings, communities of diverse immune cells, including T and B cells, often accompanied by antigen presenting cells, have been described to aggregate into tertiary lymphoid structures (TLS) or TLS-like neighborhoods, 94 which are thought to promote T-and B-cell anti-tumor memory and effector activity. [95][96][97][98][99][100][101][102] Multiple recent studies of the spatial relationships of immune cells in cancer have pointed toward stemlike CD8+ T cells expressing PD-1 and TCF-1/TCF-7 as a hub for anti-tumor immunity, often in complex with T helper and myeloid cell populations, such as dendritic cells.…”

“…[95][96][97][98][99][100][101][102] Multiple recent studies of the spatial relationships of immune cells in cancer have pointed toward stemlike CD8+ T cells expressing PD-1 and TCF-1/TCF-7 as a hub for anti-tumor immunity, often in complex with T helper and myeloid cell populations, such as dendritic cells. 90,92,[103][104][105][106] For myeloid malignancies, however, such immune networks have been only minimally evaluated (for example, in the pediatric AML setting 107 ) in part due to the technical obstacles of applying high dimensional sequencing and spatial profiling approaches to marrow tissue that has been conventionally processed using harsh decalcification procedures, though advancing technologies and analytical methods may overcome this challenge. [108][109][110] The response of AML to immunotherapies such as ICB have been disappointing, 65,111 and defining the role of TLS-like structures or other cellular networks could serve to advance our understanding of the critical cellular players needed to coordinate an effective anti-leukemia response.…”

Quality Control for Single Cell Analysis of High-plex Tissue Profiles using CyLinter

“…Such data are powerful complements to that obtained from dissociative methods such as scRNA-seq 12–14 . Imaging approaches compatible with the formaldehyde-fixed, paraffin-embedded (FFPE) specimens universally acquired for clinical diagnosis are particularly powerful because they can tap into large archives of human biopsy and resection specimens 15,16 and also assist in the study of mouse models of disease 17 .…”