Partial Depletion of Regulatory T Cells Does Not Influence the Inflammation Caused by High Dose Hemi-Body Irradiation

Ma, Shihong; Richardson, James A.; Bitmansour, Andrew; Solberg, Timothy D.; Pidikiti, Rajesh; Song, Kwang; Stojadinovic, Strahinja; Vitetta, Ellen S.; Meyer, Jeffrey J.
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
There is clinical interest in the modulation of regulatory T cells for cancer therapy. The safety of these therapies in combination with conventional anti-cancer therapies, including radiation therapy, can be studied in animal models. The effects of partial depletion of regulatory T (Treg) cells with an anti-CD25 antibody in conjunction with ionizing radiation on inflammation and tissue injury were analyzed in C57BL/6 mice. An anti-CD25 antibody (PC61) was administered 3 days prior to 13 Gy lower-half hemi-body irradiation (HBI). The blood, spleen, mesenteric lymph nodes (mLNs) and inguinal lymph nodes (iLNs) were harvested at various times thereafter. Alterations in the proportion of leukocyte subsets including CD4+ T cells, CD8+ T cells, Treg cells, B cells, NK cells, NK1.1+ T cells, macrophages and granulocytes were analyzed by FACS. The lungs, liver, pancreas, stomach, jejunum, duodenum, ileum, colon and kidney were harvested and studied by H&E staining. Expression of inflammatory mediators in plasma and tissue were investigated by ELISA. HBI significantly decreased the leukocyte pool though the various leukocyte subsets had different sensitivities to HBI. The administration of PC61 significantly decreased the proportion of Treg cells in spleen, iLN, mLN and blood (reduction of approximately 60%). Irradiation significantly increased the proportion of Treg cells in the spleen, iLN and mLN. HBI induced a systemic inflammatory reaction as demonstrated by increased plasma levels of IL-6, KC/CXCL1 and circulating granulocytes in the blood. Neutrophils also infiltrated the small bowel. The same general patterns were observed whether or not Treg cells were partially depleted with PC61 prior to HBI. These data demonstrate that partial depletion of Treg cells in these mice does not influence HBI-induced inflammatory response and tissue injury, and that combining anti-CD25 therapy with radiation may be safe and well tolerated in a clinical setting.


Related Articles

  • Anti-Tumor Effects of Ganoderma lucidum (Reishi) in Inflammatory Breast Cancer in In Vivo and In Vitro Models. Suarez-Arroyo, Ivette J.; Rosario-Acevedo, Raysa; Aguilar-Perez, Alexandra; Clemente, Pedro L.; Cubano, Luis A.; Serrano, Juan; Schneider, Robert J.; Martínez-Montemayor, Michelle M. // PLoS ONE;Feb2013, Vol. 8 Issue 2, p1 

    The medicinal mushroom Ganoderma lucidum (Reishi) was tested as a potential therapeutic for Inflammatory Breast Cancer (IBC) using in vivo and in vitro IBC models. IBC is a lethal and aggressive form of breast cancer that manifests itself without a typical tumor mass. Studies show that IBC...

  • A High-throughput Pharmacoviral Approach Identifies Novel Oncolytic Virus Sensitizers. Diallo, Jean-Simon; Le Boeuf, Fabrice; Lai, Frances; Cox, Julie; Vaha-Koskela, Markus; Abdelbary, Hesham; MacTavish, Heather; Waite, Katherine; Falls, Theresa; Wang, Jenny; Brown, Ryan; Blanchard, Jan E.; Brown, Eric D.; Kirn, David H.; Hiscott, John; Atkins, Harry; Lichty, Brian D.; Bell, John C. // Molecular Therapy;Jun2010, Vol. 18 Issue 6, p1123 

    Oncolytic viruses (OVs) are promising anticancer agents but like other cancer monotherapies, the genetic heterogeneity of human malignancies can lead to treatment resistance. We used a virus/cell-based assay to screen diverse chemical libraries to identify small molecules that could act in...

  • Unleashing antitumor T-cell activation without ensuing autoimmunity: the case for A20-deletion in adoptive CD8 T-cell therapy. Verdeil, Grégory; Schmitt-Verhulst, Anne-Marie // OncoImmunology;Oct2014, Vol. 3 Issue 10, pN.PAG 

    Mechanisms controlling immune reactivity prevent excessive inflammation and autoimmunity, but generally dampen antitumor activity. We recently showed that adoptively transferred antitumor CD8+T cells harboring a deletion of A20/Tnfaip3, a molecule controlling NF-κB activation, possessed...

  • Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study. Iles, S M; Gollins, S W; Susnerwala, S; Haylock, B; Myint, S; Biswas, A; Swindell, R; Levine, E; Iles, Sm; Gollins, Sw // British Journal of Cancer;3/24/2008, Vol. 98 Issue 7, p1210 

    In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic...

  • Lack of Cetuximab induced skin toxicity in a previously irradiated field: case report and review of the literature. Kanakamedala, Madhava R.; Packianathan, Satyaseelan; Vijayakumar, Srinivasan // Radiation Oncology;2010, Vol. 5, p38 

    Introduction: Mutation, amplification or dysregulation of the EGFR family leads to uncontrolled division and predisposes to cancer. Inhibiting the EGFR represents a form of targeted cancer therapy. Case report: We report the case of 79 year old gentlemen with a history of skin cancer involving...

  • Modeling the Effects of Space Structure and Combination Therapies on Phenotypic Heterogeneity and Drug Resistance in Solid Tumors. Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît // Bulletin of Mathematical Biology;Jan2015, Vol. 77 Issue 1, p1 

    Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the...

  • Stem Cell Patents: An Innovative Approach to Anti-Cancer Drug Discovery. Navone, Stefania; Cristini, Silvia; Canzi, Laura; Parati, Eugenio A.; Invernici, Gloria // Recent Patents on Anti-Cancer Drug Discovery;Jan2010, Vol. 5 Issue 1, p14 

    Over the last decade, improvements in cancer therapies have prolonged the lives of cancer patients. Despite dramatic advances in imaging technology, surgical techniques, and adjuvant radio - and chemotherapy, the overall prognosis of this disease remains dismal. In light of this, there is an...

  • Trial watch: Dendritic cell-based anticancer therapy. Bloy, Norma; Pol, Jonathan; Aranda, Fernando; Eggermont, Alexander; Cremer, Isabelle; Fridman, Wolf Hervé; Fučíková, Jitka; Galon, Jérôme; Tartour, Eric; Spisek, Radek; Dhodapkar, Madhav V.; Zitvogel, Laurence; Kroemer, Guido; Galluzz, Lorenzo i // OncoImmunology;Nov2014, Vol. 3 Issue 11, pN.PAG 

    The use of patient-derived dendritic cells (DCs) as a means to elicit therapeutically relevant immune responses in cancer patients has been extensively investigated throughout the past decade. In this context, DCs are generally expanded, exposed to autologous tumor cell lysates or loaded with...

  • Cracking the glioma-NK inhibitory code: toward successful innate immunotherapy. Lowenstein, Pedro R; Baker, Gregory J.; Castro, Maria G. // OncoImmunology;Nov2014, Vol. 3 Issue 11, pN.PAG 

    Natural killer (NK) cells eradicate galectin-deficient malignant gliomas without the necessity for T cell cooperation. This phenomenon was discovered as a consequence of reducing glioma-derived galectin-1. We propose that stimulation of endogenous antitumor NK cell activity may be achieved by...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics