Loss of CTL function among high-avidity tumor-specific CD8+ T cells following tumor infiltration

Cancer Research
Claire N JanickiDavid J Morgan

Abstract

A major problem in generating effective antitumor CTL responses is that most tumors express self-antigens to which the immune system is rendered unresponsive due to mechanisms of self-tolerance induction. CTL precursors (CTLp) expressing high-affinity T-cell receptors (TCR) are often functionally deleted from the repertoire, leaving a residual repertoire of CTLp having only low-affinity TCR. Furthermore, even when unique antigens are expressed, their presentation by dendritic cells (DC) may predispose to peripheral tolerance induction rather than the establishment of CTL responses that kill tumor cells. In this study, we examined both high-avidity (CL4) and low-avidity (CL1) CD8(+) T-cell responses to a murine renal carcinoma expressing, as a neoantigen, high and low levels of the hemagglutinin (HA) protein from influenza virus A/PR/8 H1N1 (PR8; RencaHA(high) and RencaHA(low)). Our data show that, following encounter with K(d)HA epitopes cross-presented by bone marrow-derived DC, low-avidity CL1 cells become tolerized within tumor-draining lymph nodes (TDLN), and in mice bearing either RencaHA(high) or RencaHA(low) tumors, very few form tumor-infiltrating lymphocytes (TIL). In marked contrast, high-avidity CL4 cells differentia...Continue Reading

Citations

Sep 28, 2010·Archivum Immunologiae Et Therapiae Experimentalis·Nejat K Egilmez, Mehmet O Kilinc
Mar 10, 2009·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Christiane GeigerDolores J Schendel
Oct 4, 2008·Journal of Immunotherapy·Anna Karolina PaluckaJacques Banchereau
Apr 8, 2009·Critical Reviews in Immunology·Hideho OkadaMitsugu Fujita
Oct 28, 2009·World Journal of Gastroenterology : WJG·Hans-Udo KasperAnton Gillessen
Apr 18, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joanne BoldisonLindsay B Nicholson
Dec 21, 2013·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Arthur A HurwitzZiqiang Zhu
Apr 12, 2014·Acta Neuropathologica·Rainer Glass, Michael Synowitz
Sep 5, 2008·Expert Review of Vaccines·Thomas M Luby
Dec 5, 2015·Frontiers in Immunology·Michael HebeisenNathalie Rufer
Sep 8, 2011·International Journal of Cancer. Journal International Du Cancer·Anna N MendlerElfriede Noessner
Apr 8, 2010·European Journal of Immunology·Alison M McDonnellAndrew J Currie
Nov 4, 2015·The Journal of Experimental Medicine·Douglas C PalmerNicholas P Restifo
Dec 9, 2014·Human Vaccines & Immunotherapeutics·Jessica E Thaxton, Zihai Li
Jul 22, 2011·Leukemia Research·Deepa K KrishnadasKenneth G Lucas
Jul 23, 2013·Blood·Chiara Bonini, Anna Mondino
Mar 30, 2010·Immunology Letters·Jason BrayerEduardo M Sotomayor
Aug 14, 2012·Critical Reviews in Oncology/hematology·Ivan Diaz-PadillaAna Oaknin
Mar 21, 2017·Frontiers in Cell and Developmental Biology·Elfriede Noessner
Sep 22, 2011·British Journal of Cancer·K HottaY Nakajima
Sep 27, 2019·Frontiers in Immunology·Kalliopi IoannidouDaniel E Speiser
Oct 6, 2017·Oncotarget·Michael Bruns, Wolfgang Deppert
Dec 16, 2019·Cellular and Molecular Life Sciences : CMLS·Ziqiang WangWeiren Huang
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanjun LiuYukai He
May 11, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Petra U PrinzElfriede Noessner
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mehmet O KilincNejat K Egilmez
Jan 25, 2014·Cancer Immunology Research·Stephanie K DouganHidde L Ploegh
Jun 22, 2017·Cancer Immunology Research·Christopher D ZahmDouglas G McNeel
Dec 4, 2012·Cancer Research·Ziqiang ZhuArthur A Hurwitz
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Patricia Castro-SanchezRose Zamoyska

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.