Substantially Modified Ratios of Effector to Regulatory T Cells During Chemotherapy in Ovarian Cancer Patients Return to Pre-Treatment Levels at Completion: Implications for Immunotherapy

Park, Anthony; Govindaraj, Chindu; Xiang, Sue D.; Halo, Julene; Quinn, Michael; Scalzo-Inguanti, Karen; Plebanski, Magdalena

doi:10.3390/cancers4020581

Cited by 12 publications

(14 citation statements)

References 46 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cancer patients, carboplatin/paclitaxel therapy decreases the proportion of circulating regulatory T cells after around 12–14 days . However, the immunologic effects are eventually restored to initial pre‐chemotherapy values despite repeated chemotherapy . These findings suggest the possible need for immunologic interventions that will break the existing homeostatic mechanisms of immune escape.…”

Section: Discussionmentioning

confidence: 99%

“…16 However, the immunologic effects are eventually restored to initial pre-chemotherapy values despite repeated chemotherapy. 17 These findings suggest the possible need for immunologic interventions that will break the existing homeostatic mechanisms of immune escape. Immunologic examinations of tissue biopsy specimens before and after nivolumab failure may shed light on this issue.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

et al. 2017

View full text Add to dashboard Cite

Promising outcomes of salvage chemotherapy after nivolumab therapy have been reported; however, little is known about the detailed clinical and immunologic features in lung cancer patients in whom nivolumab is unsuccessful. We report two cases of nivolumab‐refractory lung cancer, in which chemotherapy resulted in rapid regression of the lung cancer. Upon initial diagnosis, the biopsy specimens showed PD‐ligand 1 (PD‐L1)‐expressing cancer cells, accompanied by tumor‐infiltrating lymphocytes with a favorable CD8/CD4 ratio. Immunosuppressive regulatory T cells and cells positive for TIM‐3 were also observed. Physicians should take caution in treating lung cancer patients after progression on nivolumab. Further studies with a large cohort are warranted to identify the patients that may benefit from salvage chemotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Although various changes regarding the proportion and/or activation status of T‐cell subsets in peripheral blood caused by chemotherapy have been reported in several malignant tumors, including thoracic malignancies, ovarian cancers, and pancreatic cancers, it still remains unclear how TPF induction chemotherapy against HNSCC modulates the immune cell profile. During chemotherapy, the peripheral immune cell profile regulated by complex homeostatic mechanisms could be influenced by a variety of factors, including the type of chemotherapeutic agents, clinical pharmacokinetics and pharmacodynamics of chemotherapeutic agents, and their differences in sensitivity to chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 99%

“…For evaluation of the activation status in immune cells, CD38 was used as an activation marker in T cells. CD38 is a multifunctional protein that serves as both an antigen and an enzyme, and it has been used as a marker for T and B cell activation and differentiation …”

mentioning

confidence: 99%

Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: Immunomodulatory effects of chemotherapy

et al. 2016

View full text Add to dashboard Cite

Tumor cells have evolved sophisticated means of escape from the host immune system. To date, several important immunological phenomena have been revealed in peripheral blood as well as within tumors. In the present study, we first investigated the proportion and activation status of peripheral immune regulatory cells and CD8+ T‐cell subsets in patients with head and neck squamous cell carcinoma (HNSCC) using a multicolor flow cytometer, and then evaluated how therapy with docetaxel, cisplatin, and 5‐fluorouracil modulated the immune cell profile in peripheral blood. The proportion of naïve T cells was lower and that of effector memory T cells (TEM) was higher in HNSCC patients than in healthy donors. Moreover, the proportions of activated TEM cells and effector T cells (TEFF) were dramatically increased in patients with advanced stage disease. The proportion of regulatory T cells and CD14+HLA‐DR− myeloid‐derived suppressor cells was elevated in HNSCC patients. Of note, after therapy, in addition to the transient reduction in immune regulatory cells, decreases in central memory T cells and increases in TEFF cells were observed among CD8+ T‐cell subsets, suggesting differentiation from central memory T cells into TEFF cells. Our results suggested that, despite the immunosuppressive status in HNSCC patients, tumor‐specific immune responses mediated by CD8+ T cells might be induced and maintained. Moreover, chemotherapy can trigger not only a transient reduction in immune regulatory cells but also further activation of CD8+ T cells.

show abstract

“…Drug Discovery: Recent Progress and the Future Regular Article 0, 14 (range, days [11][12][13][14][15][16], and 21 (range, days 21-36) and from those treated with EGFR-TKI on days 0, 14 (range, days 13-18), and 28 (range, days 28-52). Peripheral blood mononuclear cells (PBMC) were isolated by gradient density centrifugation using Lymphoprep (Axis Shield, U.K.).…”

Section: Current Topicsmentioning

confidence: 99%

Docetaxel Upregulates HMGB1 Levels in Non-small Cell Lung Cancer

Haruna

Hirata

Iwahori

et al. 2020

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) exert beneficial effects in non-small cell lung cancer (NSCLC) patients. However, ICIs are only advantageous for a limited population of NSCLC patients. Therefore to enhance their effects, combination therapies with ICIs have been developed. To identify preferable chemotherapy to combine with ICIs against lung cancer, we examined immunological effects of docetaxel compared with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We found no difference in peripheral lymphocyte counts and ratio of their subpopulations in lung cancer patients before and after both treatments. On the other hand, plasma levels of high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) protein, showed significant increase after docetaxel treatment. Furthermore, we investigated effects of HMGB1 on tumor-infiltrating immune cells obtained from surgically resected tumor tissue from NSCLC patients. When the tumor infiltrating cells were stimulated with HMGB1, CD11c cells showed increased expression of activation markers. These findings imply that docetaxel could be involved in anti-tumor immunity via HMGB1. Therefore docetaxel might be a candidate for combination treatment with ICIs.

show abstract

Substantially Modified Ratios of Effector to Regulatory T Cells During Chemotherapy in Ovarian Cancer Patients Return to Pre-Treatment Levels at Completion: Implications for Immunotherapy

Cited by 12 publications

References 46 publications

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

Dynamic changes in immune cell profile in head and neck squamous cell carcinoma: Immunomodulatory effects of chemotherapy

Docetaxel Upregulates HMGB1 Levels in Non-small Cell Lung Cancer

Contact Info

Product

Resources

About