Low Total Lymphocyte Count Is Associated with Poor Survival in Patients with Resected Pancreatic Adenocarcinoma Receiving a GM-CSF Secreting Pancreatic Tumor Vaccine

Abstract

Background Low total lymphocyte count (TLC) and lymphocyte-to-neutrophil ratio have been found to be poor prognostic indicators in several different tumor types at various stages. Although immune-based therapies are under rapid development, it is not known whether baseline complete blood counts, particularly lymphocytes, are associated with the clinical outcomes of patients receiving immunotherapies. Methods We performed a retrospective analysis of complete blood count for 59 patients enrolled onto a phase II trial evaluating the integration of an adjuvant immunotherapy—irradiated granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic pancreatic tumor vaccine (GVAX)—with standard chemoradiation. Results After adjusting for nodal status, individuals with a TLC of <1,500 cells/mm3 (10 patients) had significantly higher risk, both in terms of overall survival (OS) [adjusted hazard ratio 2.63, 95 % confidence interval (CI) 1.22–5.67, p = 0.013] and progression-free survival (adjusted hazard ratio 3.07, 95 % CI 1.03–6.93, p = 0.003), compared to those with a TLC of ≤1,500 cells/mm3 (49 patients). Adjuvant chemoradiation significantly reduced lymphocyte counts from baseline values. Patients with suppression of their lymphocytes to <500 cells/mm3 after chemoradiation also had shorter disease-free and OS. Conclusions Immunosuppressive conditions associated with surgical procedures and chemoradiation may affect the efficacy of immunotherapy.

Prognostic Significance of Preoperative Prognostic Nutritional Index in Epithelial Ovarian Cancer Patients Treated with Platinum-Based Chemotherapy

“…It has been detected that serum albumin is a stable predictor of prognosis during initial treatment in patients with diffuse large B cell lymphoma, and the preoperative albumin-to-globulin ratio has been verified to have predictive value for long-term mortality in nasopharyngeal carcinoma [15,16]. The peripheral lymphocyte count, as a component of the complete blood count, together with the neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio, has been reported to be a critical factor associated with OS in many types of cancers [17,18,19]. It is a parameter of cell-mediated immunity which is important for the host defense against cancer, and a low lymphocyte count may be associated with immune suppression indicating an inadequate immunological response.…”

B7‐H5/CD28H is a co‐stimulatory pathway and correlates with improved prognosis in pancreatic ductal adenocarcinoma

“…CD3 and CD8 were employed for tumor infiltrated lymphocytes (TIL) markers, and Image J (version Java 1.8.0_112, NIH, Bethesda, MD, USA) analysis was performed for measurement of positive staining cells. More than 1500 cells/mm 3 CD3 + or CD8 + T cells was defined as high TIL status, otherwise would be defined as low TIL, as previously reported …”

“…More than 1500 cells/mm 3 CD3 + or CD8 + T cells was defined as high TIL status, otherwise would be defined as low TIL, as previously reported. 16,17 For the ELISAs, tumor cells and CD8 + naïve T cells co-culture supernatants were collected by centrifugation and stored at −80°C.…”

PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors

“…27 Phase I and II clinical trials of this vaccine demonstrated its safety and its ability to enhance tumor antigen (mesothelin)-specific interferon-γ (IFNγ) producing T cells in peripheral lymphocytes, which correlated with prolonged survival. 27-32 More recently, through a clinical trial of GVAX as a neoadjuvant therapy for resectable PDAs, we observed vaccine-induced tertiary lymphoid aggregates in PDAs surgically resected from the majority of patients who received the vaccine therapy two weeks prior to the surgery and also observed the infiltration of PD-L1 + cells within these lymphoid aggregates. 33 …”