Dynamics of T‐cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T‐cells

Fialová, Alena; Partlová, Simona; Sojka, Ludek; Hromadkova, Hana; Brtnicky, Tomas; Fučíková, Jitka; Kocián, Petr; Rob, Lukáš; Bartůňková, Jiřina; Špíšek, Radek

doi:10.1002/ijc.27759

Cited by 92 publications

(89 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…17 Further, Fialova et al showed a transition from a strong Th17 immune response in early cancer stages to a dominant population of Tregs by late stages in ovarian cancer patient samples, suggesting tumor progression sculpts Treg involvement in the local immune environment. 51 Even after treatment with neo-adjuvant chemotherapy, lower FOXP3CTreg infiltration is correlated with increased survival. 52 In contrast to above studies, a recent evaluation of tumor specimens from 73 ovarian cancer patients found that Treg frequency was a positive prognostic factor and no association could be made with other TILs.…”

Section: Regulatory T-cells and Survival Impact In Ovarian Cancermentioning

confidence: 99%

Tumor infiltrating lymphocytes in ovarian cancer

Santoiemma

Powell

2015

Cancer Biology & Therapy

292

229

View full text Add to dashboard Cite

The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and geneengineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment. IntroductionTumor infiltrating lymphocytes (TILs) are present in ovarian cancer and are prognostic for increased survival. Given the impact of immunomodulatory regimens in melanoma, renal cell carcinoma, and lung cancer, and the recent elucidation of bona fide tumor-reactive TILs in ovarian cancer, the development of approaches that mobilize tumor-reactive TILs for successful eradication of ovarian cancer is now a high priority. In spite of strong rationale, attempts at administration of adoptive T cell transfer, immune enhancing antibody, and tumor immune environment conditioning in ovarian cancer have been minimal with some positive results reported in patients. In light of the recent development of new immunotherapeutic agents and treatment regimens that bolster host TIL activity, we review the current understanding of the immunobiology of human ovarian cancer including the impact of TIL subset accumulation on ovarian cancer survival and the effect of immune activation in the tumor microenvironment, and conclude that a new line of cancer immunotherapy investigations is warranted in ovarian carcinoma.Ovarian cancer is the second most common and most lethal gynecologic malignancy in the United States with approximately 22,000 new cases and 14,000 deaths expected in 2013.1 Ovarian cancer is often diagnosed at an advanced stage, with the large majority of new cases spread past the primary site. Since there are no current recommendations for ovarian cancer screenings, most efforts at combating ovarian cancer have been targeted at the discovery of new treatments rather than preventative measures. Currently, surgical staging and cytoreduction followed by chemotherapy is the mainstay of treatment, although in some cases neo-adjuvant chemotherapy is attempted.2 The standard for surgical staging consists of total hysterectomy and bilateral salpingooophrectomy with pelvic and para-aortic lymph node di...

show abstract

Section: Regulatory T-cells and Survival Impact In Ovarian Cancermentioning

confidence: 99%

Tumor infiltrating lymphocytes in ovarian cancer

Santoiemma

Powell

2015

Cancer Biology & Therapy

292

229

View full text Add to dashboard Cite

show abstract

“…Tumor-infiltrating immune cells have been described in most solid tumors (3,4). The type, the density, and the location of immune cells in the tumor microenvironment, defined as immune contexture strongly affect the prognosis of cancer patients (4)(5)(6)(7). In non-small cell lung cancer (NSCLC), a high density of mature dendritic cells (DC) correlates with long-term survival of the patients (8) and with a strong infiltration by CD8 þ T cells that are predominantly of the effector-memory phenotype (9).…”

Section: Introductionmentioning

confidence: 99%

Calreticulin Expression in Human Non–Small Cell Lung Cancers Correlates with Increased Accumulation of Antitumor Immune Cells and Favorable Prognosis

et al. 2016

View full text Add to dashboard Cite

A high density of tumor-infiltrating mature dendritic cells (DC) and CD8þ T cells correlates with a positive prognosis in a majority of human cancers. The recruitment of activated lymphocytes to the tumor microenvironment, primed to recognize tumor-associated antigens, can occur in response to immunogenic cell death (ICD) of tumor cells. ICD is characterized by the preapoptotic translocation of calreticulin (CRT) from the endoplasmic reticulum (ER) to the cell surface as a result of an ER stress response accompanied by the phosphorylation of eukaryotic initiation factor 2a (eIF2a). We conducted a retrospective study on two independent cohorts of patients with non-small cell lung cancer (NSCLC) to investigate the prognostic potential of CRT. We report that the level of CRT expression on tumor cells, which correlated with eIF2a phosphorylation, positively influenced the clinical outcome of NSCLC. High CRT expression on tumor cells was associated with a higher density of infiltrating mature DC and effector memory T-cell subsets, suggesting that CRT triggers the activation of adaptive immune responses in the tumor microenvironment. Accordingly, patients with elevated CRT expression and dense intratumoral infiltration by DC or CD8 þ T lymphocytes had the best prognosis. We conclude that CRT expression constitutes a new powerful prognostic biomarker that reflects enhanced local antitumor immune responses in the lung.

show abstract

“…Fialová et al suggested that the development of antitumor immune responses in ovarian cancer patients is highly dynamic. The recruitment of Th17 cells with higher IL17 and IL21 expression levels in ovarian cancer tissues has been reported in the early stages of disease (Fialová et al 2013), and a lower level of IL17 has been reported in more advanced ovarian cancer-associated ascites (Kryczek et al 2009). The expression levels of IL17a and IL21 in Receiver operating characteristic (ROC) curves of the overall score for disease relapse (A) and disease-related death (B) of ovarian cancer patients in the derivation group (NTUH set), validation group (NCKUH set), and all patients.…”

Section: Discussionmentioning

confidence: 99%

IL17a and IL21 combined with surgical status predict the outcome of ovarian cancer patients

Chen¹,

Chou²,

Chang³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

Aside from tumor cells, ovarian cancer-related ascites contains the immune components. The aim of this study was to evaluate whether a combination of clinical and immunological parameters can predict survival in patients with ovarian cancer. Ascites specimens and medical records from 144 ovarian cancer patients at our hospital were used as the derivation group to select target clinical and immunological factors to generate a risk-scoring system to predict patient survival. Eighty-two cases from another hospital were used as the validation group to evaluate this system. The surgical status and expression levels of interleukin 17a (IL17a) and IL21 in ascites were selected for the risk-scoring system in the derivation group. The areas under the receiver operating characteristic (AUROC) curves of the overall score for disease-free survival (DFS) of the ovarian cancer patients were 0.84 in the derivation group, 0.85 in the validation group, and 0.84 for all the patients. The AUROC curves of the overall score for overall survival (OS) of cases were 0.78 in the derivation group, 0.76 in the validation group, and 0.76 for all the studied patients. Good correlations between overall risk score and survival of the ovarian cancer patients were demonstrated by sub-grouping all participants into four groups (P for trend !0.001 for DFS and OS). Therefore, acombination of clinical and immunological parameters can provide a practical scoring system to predict the survival of patients with ovarian carcinoma. IL17a and IL21 can potentially be used as prognostic and therapeutic biomarkers.

show abstract

Dynamics of T‐cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T‐cells

Cited by 92 publications

References 58 publications

Tumor infiltrating lymphocytes in ovarian cancer

Tumor infiltrating lymphocytes in ovarian cancer

Calreticulin Expression in Human Non–Small Cell Lung Cancers Correlates with Increased Accumulation of Antitumor Immune Cells and Favorable Prognosis

IL17a and IL21 combined with surgical status predict the outcome of ovarian cancer patients

Contact Info

Product

Resources

About