Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes

Milne, Katy; Alexander, Cheryl; Webb, John R.; Sun, Winnie; Dillon, Kristy; Kalloger, Steve E.; Gilks, C. Blake; Clarke, Blaise A.; Köbel, Martin; Nelson, Brad H.

doi:10.1186/1479-5876-10-33

Cited by 105 publications

(85 citation statements)

References 43 publications

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“…Milne et al [35] failed to document correlation between the lymphocyte count in peripheral blood and CD8(+) or CD20(+) TIL in h ovarian cancer patients, he found significant correlation of both lymphocyte count and TIL with prognosis, but the correlations were independent of each other, but in our study we are the first to find correlation between the pre CRT peripheral lymphocytes subsets and tissue expression of CD4 & 8 in rectal cancer patients. We see significant positive correlation between pre CRT peripheral lymphocyte, T lymphocytes, Th, Tc and tissue CD4 & CD8 and all were statistically significant correlated to tumor regression rate.…”

Section: Discussioncontrasting

confidence: 68%

Peripheral and Tissue Lymphocytes as Predictors of Pathological Response in Locally Advanced Rectal Cancer Post Neoadjuvant Chemoradiotherapy

Shorbagy¹,

Elfarargy²,

Salem³

et al. 2017

JCT

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Background: Tailoring therapy is the target in the management of any cancer; if factors which can predict response to treatment are identified, we can individualize treatment. Locally advanced rectal cancer studies reported that tumor microenvironment and host immune response played roles in sensitivity to chemoradiotherapy (CRT) by proving that both peripheral circulating lymphocytes and tumor infiltrating lymphocytes (TILs) strongly correlated with the response rate to CRT and it impacted disease outcome. Aim of the work: We aimed to assess the predictive value of peripheral blood lymphocytes and tumor infiltrating lymphocytes by correlation with regression rate post chemo-radiotherapy in patients with rectal cancer, and to find correlation between peripheral and tissue lymphocytes. Method: Before neoadjuvant, CRT venous blood samples were obtained from 40 patients with rectal cancer, and prior to surgery. Blood cell counts in the samples were analyzed using an au- 251helper, and T cytotoxic lymphocytes with significant p value for all. Conclusion: We concluded that peripheral lymphocytic count and its subsets have significant correlation to tissue CD4, CD8 and both can predict pathological response to CRT; enhancement of lymphocytes mediated immune response can help for outcome improvement.

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Section: Discussioncontrasting

confidence: 68%

Peripheral and Tissue Lymphocytes as Predictors of Pathological Response in Locally Advanced Rectal Cancer Post Neoadjuvant Chemoradiotherapy

Shorbagy¹,

Elfarargy²,

Salem³

et al. 2017

JCT

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“…17 Similar results have been reported extensively elsewhere. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Three other studies indicate that both CD3 and CD8C TILs are of good prognosis in ovarian cancer. [32][33][34] While CD8C TILs appear to be best associated with improved survival, still other reports indicate that CD4C TILs are the subset of value in prognosticating ovarian cancer.…”

Section: Background On Tumor Infiltrating Lymphocytesmentioning

confidence: 99%

Tumor infiltrating lymphocytes in ovarian cancer

Santoiemma

Powell

2015

Cancer Biology & Therapy

295

229

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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...

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“…5 respectively). 6 The total number of lymphocytes has also been shown to be prognostic 7 The tumour microenvironment uses several mechanisms to evade anti-tumour immune responses. Programmed cell death ligand 1 (PD-L1) is highly up-regulated on some tumour cells as well as immune cells and has been implicated in tumour immune homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer

Chatterjee

Dai

Aziz

et al. 2017

Clinical Cancer Research

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Purpose: We aimed to establish whether programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, in ovarian cancer tumor tissue and blood, could be used as biomarkers for discrimination of tumor histology and prognosis of ovarian cancer. Experimental Design: Immune cells were separated from blood, ascites, and tumor tissue obtained from women with suspected ovarian cancer and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumor-associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses. Results: Biomarkers from the discovery cohort that associated with PD-L1+ cells were found. PD-L1+ CD14+ cells and PD-L1+ CD11c+ cells in the monocyte gate showed a distinct expression pattern when comparing benign tumors and epithelial ovarian cancers (EOCs)—confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+ and PD-L1+ CD14+ cells in the monocyte gate performed better than the well-established tumor marker CA-125 alone. Plasma soluble PD-L1 was elevated in patients with EOC compared with healthy women and patients with benign ovarian tumors. Low total PD-1+ expression on lymphocytes was associated with improved survival. Conclusions: Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti–PD-1/PD-L1 therapy in ovarian cancer. Clin Cancer Res; 23(13); 3453–60. ©2016 AACR.

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Absolute lymphocyte count is associated with survival in ovarian cancer independent of tumor-infiltrating lymphocytes

Cited by 105 publications

References 43 publications

Peripheral and Tissue Lymphocytes as Predictors of Pathological Response in Locally Advanced Rectal Cancer Post Neoadjuvant Chemoradiotherapy

Peripheral and Tissue Lymphocytes as Predictors of Pathological Response in Locally Advanced Rectal Cancer Post Neoadjuvant Chemoradiotherapy

Tumor infiltrating lymphocytes in ovarian cancer

Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer

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