Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official VSports app下载. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure V体育官网. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. .

. 2013 Nov;19(11):1537-45.
doi: 10.1016/j.bbmt.2013.08.010. Epub 2013 Sep 6.

Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part I. Biology of relapse after transplantation

Ronald E Gress  1 , Jeffrey S Miller, Minoo Battiwalla, Michael R Bishop, Sergio A Giralt, Nancy M Hardy, Nicolaus Kröger, Alan S Wayne, Dan A Landau, Catherine J Wu
Affiliations

Proceedings from the National Cancer Institute's Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part I. Biology of relapse after transplantation

Ronald E Gress et al. Biol Blood Marrow Transplant. 2013 Nov.

Abstract

In the National Cancer Institute's Second Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Biology of Relapse discussed recent advances in understanding some of the host-, disease-, and transplantation-related contributions to relapse, emphasizing concepts with potential therapeutic implications. Relapse after hematopoietic stem cell transplantation (HSCT) represents tumor escape, from the cytotoxic effects of the conditioning regimen and from immunologic control mediated by reconstituted lymphocyte populations. Factors influencing the biology of the therapeutic graft-versus-malignancy (GVM) effect-and relapse-include conditioning regimen effects on lymphocyte populations and homeostasis, immunologic niches, and the tumor microenvironment; reconstitution of lymphocyte populations and establishment of functional immune competence; and genetic heterogeneity within the malignancy defining potential for clonal escape VSports手机版. Recent developments in T cell and natural killer cell homeostasis and reconstitution are reviewed, with implications for prevention and treatment of relapse, as is the application of modern genome sequencing to defining the biologic basis of GVM, clonal escape, and relapse after HSCT. .

Keywords: Allogeneic; Biology; Prevention; Relapse; Stem cell transplantation; Treatment. V体育安卓版.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Diagrammatic representation of the timeline of immune reconstitution in a 40 year old, CMV seropositive adult
Following cytoreductive therapy, the peripheral CD4 and CD8 T cell populations are severely depleted. The thymus is reduced to a small remnant (shown at 1.5 month post-transplant). CD4 and CD8 T cells immediately undergo a marked expansion in response to homeostatic cytokines and endogenous antigens, generating a population that is mainly composed of memory (green) and effector (orange) T cells, with few naïve (blue) or TREC-bearing cells (also represented at 1.5 month post-transplant). The CD4:CD8 ratio becomes inverted by the more rapid expansion of CD8+ T cells, demonstrated by the peak of (orange) effector CD8 cells as compared to the smaller (green) peak of CD4+ cells at 1.5 months. TCR repertoire diversity that has been lost by lymphodepletion, is further skewed by oligoclonal expansion of the limited number of remaining cells. The expanded population of CD8 T cells persists and may continue to dominate the CD8 TCR repertoire as shown in subsequent months by the large effector (orange) CD8 population. Renewed thymopoiesis begins within the first 6 months, but the full contribution of naïve, TREC-bearing T cells with a diverse TCR repertoire may require 1 – 2 years to be evident. *Reprinted from Seminars in Immunology, Vol 19 No 5, K. M. Williams, F. T. Hakim, R. E. Gress, T cell immune reconstitution following lymphodepletion, 318-30, 2007, Copyright (2007), with permission from Elsevier.
Figure 2
Figure 2. NK cells express a number of inhibitory and activating receptors that determine function
Some of these interactions are definitively established with known signaling pathways, while others are less clear. Most receptors interact with cellular targets, but CD16 delivers a potent signal by binding the Fc portion of immunoglobulin-coated targets. The ability of NK cells to kill a target is determined by the net balance of these inhibitory, activating, antibody-dependent, and adhesion interactions. *Reprinted from Biology of Blood and Marrow Transplantation, Vol 18 (1), S2–7, W.J. Murphy, P. Parham, J.S. Miller, NK cells – from bench to clinic, S2–7, 2012, Copyright (2012), with permission from Elsevier.
Figure 3
Figure 3. Potential treatment effects on clonal heterogeneity and disease behavior
Interclonal equilibrium can remain remarkably stable for years (top). However when an aggressive minor clone arises (bottom), clonal evolution begins, and can be potentially accelerated by therapy. This may be due to differential resistance of subpopulations to treatment. Additionally, a mass extinction event, such as chemotherapy, may accelerate evolution by removing the strong incumbent and allowing the fitter rising subclone to repopulate the compartment more efficiently, as sometimes seen with bottlenecks in population genetics. Adapted from Landau, D.A., et al., Evolution and impact of subclonal mutations in chronic lymphocytic leukemia, Cell, Vol 152 (4), 714–26, 2013.
See this image and copyright information in PMC

References

    1. Boyiadzis M, Memon S, Carson J, et al. Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels. Biol Blood Marrow Transplant. 2008;14:290–300. - PubMed
    1. Fagnoni FF, Oliviero B, Giorgiani G, et al. Reconstitution dynamics of plasmacytoid and myeloid dendritic cell precursors after allogeneic myeloablative hematopoietic stem cell transplantation. Blood. 2004;104:281–289. - PubMed
    1. Peggs KS, Verfuerth S, Pizzey A, et al. Reconstitution of T-cell repertoire after autologous stem cell transplantation: influence of CD34 selection and cytomegalovirus infection. Biol Blood Marrow Transplant. 2003;9:198–205. - PubMed
    1. Hakim FT, Memon SA, Cepeda R, et al. Age-dependent incidence, time course, and consequences of thymic renewal in adults. J Clin Invest. 2005;115:930–939. - PMC - PubMed
    1. Mackall CL, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE. Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol. 1996;156:4609–4616. - PubMed

"VSports" MeSH terms