scholarly journals Aggressive Thyroid Cancer is Associated With Suppressor Circulating Immunophenotype

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A855-A856
Author(s):  
Anupam Kotwal ◽  
Svetlana Bornschlegl ◽  
Michael Gustafson ◽  
Allan Dietz ◽  
Danae Anastasia Delivanis ◽  
...  
Keyword(s):  
T Cells ◽  
Thyroid Cancer ◽  
Memory T Cells ◽  
Suppressor Cells ◽  
Distant Metastases ◽  
Cancer Prognosis ◽  
Effector Memory ◽  
Ajcc Stage ◽  
Advanced Thyroid Cancer

Abstract Introduction: The influence of the immune system on follicular cell-derived thyroid cancer behavior has been suggested by various studies but this information has not been comprehensively translated into a prediction for thyroid cancer prognosis. We aimed to identify circulating immune cell profiles associated with thyroid cancer prognosis. This information would be a significant advance in the field of thyroid cancer management. Methods: We performed a single-center prospective cohort study of 32 follicular-cell derived thyroid cancer patients enrolled at the time of initial or subsequent surgery. We performed peripheral blood multi-parameter flow cytometry and collected relevant clinicopathologic, biochemical and radiologic data. We classified patients based on the AJCC TNM cancer stage, American Thyroid Association (ATA) initial risk of recurrence, and status of disease during follow-up. Results: On initial immunophenotyping, patients with aggressive/advanced thyroid cancer (ATA high risk vs. intermediate/low risk; AJCC stage 3/4 vs. 1/2; recurrence or distant metastases vs. no evidence of disease during follow-up) demonstrated increased circulating monocytes and granulocytes but decreased all lymphocytes, T cells (specifically CD4+ and gamma delta) and natural killer (NK) T-like cells. Further immunophenotyping revealed that aggressive/advanced thyroid cancer had increased circulating CD4+CD45+RO effector memory but decreased CD4+CD45+RA central memory T cells and increased regulatory T cells. Stage 3/4 thyroid cancer patients additionally had increased circulating CD33+HLADR- myeloid-derived suppressor cells (MDSCs) as compared to stage1/2. Conclusions: Aggressive thyroid cancer at presentation (AJCC stage, ATA risk category) or during follow-up (distant metastases) is characterized by a circulating immunophenotype comprising of increased immune suppressor cells (regulatory T cells, MDSCs, effector memory T cells) but decreased immune activator cells (CD4+ T cells, gamma delta T cells, NK T-like cells, central memory T cells) as compared to less aggressive thyroid cancer. This circulating immunophenotype may serve as a biomarker for cancer prognosis and guide the selection and development of novel immunotherapies for advanced thyroid cancer.

Long-Term Immunological Profile and T Cell Dynamics In Patients Treated With Allogeneic Transplantation and TK-Cells For Hematological Malignancies

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 165-165
Author(s):  
Giacomo Oliveira ◽  
Maria Teresa Lupo Stanghellini ◽  
Nicoletta Cieri ◽  
Raffaella Greco ◽  
Maddalena Noviello ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Suicide Gene ◽  
Suicide Gene Therapy ◽  
Effector Memory ◽  
Immunological Profile

Abstract Background Suicide gene therapy applied to allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the widest clinical applications of gene therapy. By the infusion of donor lymphocytes transduced to express the Herpes Simplex Virus Thymidine Kinase (TK) suicide gene, patients achieve a rapid immune reconstitution and substantial protection against tumor recurrence. TK-cells are promptly eliminated in case of graft versus host disease (GvHD), with complete resolution of the adverse reaction. In previous studies, we showed that TK-cell infusions are necessary and sufficient to promote the generation of a fast, polyclonal and full competent T cell repertoire. In the present work we characterize the immunological profile of a cohort of long-term survivors after suicide gene therapy and we studied the long-term fate of TK-cells to shed light on memory T cell dynamics after transplantation. Results We studied 14 adult patients who underwent allo-HSCT (haploidentical HSCT: n=11; HLA-identical HSCT n=3) and infusion of purified suicide-gene modified donor T cells (median dose: 1.9x107 cells/kg, range:0.9x106-2.8x108) for high-risk hematologic malignancies between 1995 and 2010. At a median follow-up of 8,7 years (range 3-17), all patients are in complete remission. Five out of 14 patients experienced GvHD in the early phase post immune reconstitution; in all cases, ganciclovir administration proved effective in abrogating the adverse reaction. No symptoms or complications related to GvHD were observed during the long-term follow up, and none of the patient is receiving immunosuppressive drugs. We observed a complete recovery of NK cells, comprising of mature (CD56+CD16+) and immature (CD56+CD16-) NK cells. Interestingly the proportion of B cells circulating long-term in patients was significantly higher than that observed in age-related healthy controls (p<0.0001). Full recovery of CD3, including CD4 and CD8 cell counts was observed in this long-term analysis. The youngest patients (age range: 22-34 years) showed naïve and memory frequencies similar to age-matched controls. Conversely, in oldest patients (age range: 44-66 years) the frequency of naïve T cells was inferior to age-matched healthy subjects (p=0.0038), and was compensated by a larger proportion of central memory and effector memory cells. Nevertheless, we observed a high percentage of recent thymic emigrants, suggesting a full recovery of thymic output not only in young but also in old patients. Stem memory CD4 and CD8 T cell counts were similar to that of healthy controls, independently from age. CMV-specific T cells, quantified by dextramer staining, were detected in CMV+ patients. TK-cells were detected in the majority of analyzed patients (90%), at low levels (median=0,43%±6,9%). Ex vivo selection of pure TK-cells after polyclonal stimulation and NGFR-purification confirmed the presence of functional transduced cells, thus directly demonstrating the ability of memory T cells to persist for years. The proportion of TK-cells detectable at the longest follow-up did not correlate with the number of infused cells, nor patients or donors’ age, but instead with the peak of TK-cells observed within the first 3 months after infusion, suggesting that antigen recognition is dominant in driving in vivo expansion and persistence of memory T cells. Of notice TK-cells could be retrieved also in patients successfully treated with ganciclovir for GvHD, thus confirming the selective action of ganciclovir only on proliferating TK-cells. Accordingly, ganciclovir sensitivity was preserved in long-term persisting TK-cells, independently from their differentiation phenotype. While infused TK-cells displayed a predominant effector memory phenotype, gene modified T cells persisting long-term were enriched for central memory (CD45RA-CD62L+) and stem memory (CD45RA+CD62L+CD95+) phenotypes, suggesting the higher ability of these T cell subsets to persist and shape the immunological profile long-term in treated patients. Conclusion These data show that a complete donor-derived immune system is restored in adult surviving long-term after suicide gene therapy. After infusion, gene modified cells persist for up to 14 years in treated patients. Further studies on TK-cell TCR repertoire and vector integrations are currently being performed to elucidate the in vivo dynamics of infused memory T cells. Disclosures: Valtolina: MolMed S.p.A: Employment. Traversari:MolMed S.p.A: Employment. Bordignon:MolMed S.p.A: Employment. Bonini:MolMed S.p.A: Consultancy.

Effector memory T cells predict atherosclerosis progression and cardiovascular events over 4 years follow-up

2017 ◽  
Vol 263 ◽  
pp. e59
Author(s):  
Andrea Baragetti ◽  
Katia Garlaschelli ◽  
Fabrizia Bonacina ◽  
Liliana Grigore ◽  
Enrico Ammirati ◽  
...  
Keyword(s):  
T Cells ◽  
Cardiovascular Events ◽  
Memory T Cells ◽  
Effector Memory ◽  
Atherosclerosis Progression ◽  
Effector Memory T Cells

scholarly journals OX40L–OX40 Signaling in Atopic Dermatitis

2021 ◽  
Vol 10 (12) ◽  
pp. 2578
Author(s):  
Masutaka Furue ◽  
Mihoko Furue
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Memory T Cells ◽  
Effector Memory ◽  
T Helper ◽  
T Helper 1 ◽  
Therapeutic Success ◽  
T Helper 2 ◽  
Promising Target ◽  
Antigen Presenting

OX40 is one of the co-stimulatory molecules expressed on T cells, and it is engaged by OX40L, primarily expressed on professional antigen-presenting cells such as dendritic cells. The OX40L–OX40 axis is involved in the sustained activation and expansion of effector T and effector memory T cells, but it is not active in naïve and resting memory T cells. Ligation of OX40 by OX40L accelerates both T helper 1 (Th1) and T helper 2 (Th2) effector cell differentiation. Recent therapeutic success in clinical trials highlights the importance of the OX40L–OX40 axis as a promising target for the treatment of atopic dermatitis.

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