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Clonality, Growth and Spread of Cancer
Published in Jeremy R. Jass, Understanding Pathology, 2020
Clonality implies that cancer, which may comprise thousands of millions of cells, originates from a single cell. The ability of a single cell to give rise to large numbers of cells is not limited to cancer. Normal tissues include a permanent set of stem cells (see Chapter 16). These are like an ancestor from the past who is continually giving birth to new children, grandchildren and great grandchildren; the descendants will pass away but the ancestor is immortal. A cancer can be traced back to an ‘immortal’ stem cell rather than to a descendant that is committed to a limited lifespan. However, most of the cells in a cancer will have a limited lifespan. In fact when one attempts to grow cells from a cancer in a laboratory, they usually die within a short period. Occasionally one cell may survive to form a ‘cell line’ that can be used for further experiments. Such a cell would be the malignant equivalent of a normal stem cell.
B Cells and Humoral Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Figure 5–1 summarizes the origin of one B cell clone. That is, the diagram shows the possible outcomes of a single B cell’s attempt to productively rearrange Ig genes and synthesize antibody. Unsuccessful cells are lost (they die). Successful cells become part of the circulating pool of resting B cells, and are available to participate in immune responses. All progeny B cells generated by mitosis of a cell having undergone one particular series of rearrangements is called a clone, since they are genetically identical. Some divergence may occur during clonal expansion, since an individual cell of a clone may class-switch or mutate its V genes differently from its siblings. Depending on one’s point of view, one may designate the progeny of these genetic events as constituting new clones, yet they all remain clonally related, since they originated from one cell. Thus, each series of immunoglobulin gene rearrangements defines a new clone, and the circulating pool of B lymphocytes is comprised of many genetically distinct clones, each of which may have anywhere from one to thousands of members. Figure 5–8 further illustrates this concept.
Involvement of HLA Cell Membrane Molecules in T Cell Immune Responses
Published in Soldano Ferrone, B. G. Solheim, HLA Typing: Methodology and Clinical Aspects, 2019
The data summarized above demonstrate that: The T cell response to foreign antigen requires co-recognition of antigen (x) together with products of the self HLA complex of the T cell donor. T helper/ amplifier cells recognize X + self D/DR products; while cytotoxic T cells are activated by × + self ABC products.This co-recognition must occur simultaneously, i.e., in the membrane of the antigen-expressing cell.The antigen-sensitive cells are clonally distributed, both with respect to antigen and restricting HLA elements.The T cell immune response to a given antigen appears more pronounced in conjunction with some, but not other, HLA products; preferential restriction.
HIVEP3 as a potential prognostic factor promotes the development of acute myeloid leukemia
Published in Growth Factors, 2023
Yanfei Tang, Guangtao Xu, Bo Hu, Yuzhang Zhu
Acute myeloid leukemia (AML) is a malignant proliferative disease of myeloid blasts of the hematopoietic system and has a high degree of heterogeneity (Chen et al. 2019). It can be clonally expanded by normal myeloid cells at a certain immature stage during the differentiation process (Bernstein et al. 1987). AML is difficult to cure, with a 5-year survival rate less than 33% (Döhner, Weisdorf, and Bloomfield 2015). The data showed that there were approximately 1 million AML patients, ultimately causing 147,000 deaths worldwide in 2015. AML is most common in the elderly, and men are more affected than women (Döhner, Weisdorf, and Bloomfield 2015). The cure rate of AML varies greatly in different age groups; in people under 60, the cure rate is about 35%, but in people over 60 it is only 10% (Döhner, Weisdorf, and Bloomfield 2015).
Homologous recombination repair deficient prostate cancer represents an immunologically distinct subtype
Published in OncoImmunology, 2022
Sandra van Wilpe, Donjetë Simnica, Peter Slootbeek, Thomas van Ee, Samhita Pamidimarri Naga, Mark A. J. Gorris, Lieke L. van der Woude, Shabaz Sultan, Rutger H. T. Koornstra, Inge M. van Oort, Winald R. Gerritsen, Leonie I. Kroeze, Michiel Simons, Geert J. L. H. van Leenders, Mascha Binder, I. Jolanda M. de Vries, Niven Mehra
Sequencing of the TCR β locus was performed on 250–500 ng of DNA as previously described.21 Sequence alignment and clonotype quantitation was performed using MiXCR (version 3.0.5).36 Clonotypes with a read count ≥ 2 were included. To account for differences in sequencing depth, TCR repertoires were normalized to 30.000 reads. Descriptive repertoire metrics (Shannon diversity and clonality) were calculated as described elsewhere.37 The Shannon index is a measure for TCR diversity, with higher values indicate higher diversity (i.e., a higher number of TCR clones and/or a more evenly distributed repertoire). The clonality (inverse measure of evenness) describes the abundance of the clones within the repertoire and ranges from 0 to 1, with 1 being a completely clonal repertoire (1 clone). TCR repertoires of 32 age- and sex-matched healthy donors (HD) were used as controls. Analyses were carried out using R (version 3.4.4) and the tcR package.38
Circulating biomarkers of response to immunotherapy and immune-related adverse events
Published in Expert Review of Molecular Diagnostics, 2022
Zachary Garrison, Noah Hornick, Jeffrey Cheng, Rajan P. Kulkarni
A more recent analysis of T-cell clonality within this context comes from Lozano et al. Their in-depth single-cell analysis of 78 metastatic melanoma patients treated with anti-PD-1 monotherapy (33) or dual anti-PD-1/anti-CTLA-4 (38) revealed elevated CD4 cell clonality in patients who developed irAEs [102]. More broadly, increased TCR repertoire in the blood was also predictive of CBI-induced irAEs. All of these studies demonstrate useful clinical information can be obtained from T-cell clonality measurements. The major drawback to this biomarker is the complexity and cost required to effectively analyze T-cell clonality. The approach employed by Lozano and others requires single-cell analysis that, in its current state, is far too time-consuming and expensive to be clinically applicable. Simpler methods for T-cell profiling are crucial to make TCR repertoire a viable biomarker for both immune therapy and risk of irAEs.