Elsevier

Surgery

Volume 131, Issue 2, February 2002, Pages 135-138
Surgery

Original Communications
Paucity of dendritic cells in pancreatic cancer*,**

https://doi.org/10.1067/msy.2002.119937Get rights and content

Abstract

Background. The number of dendritic cells (DC) in the local tumor environment correlates with patient survival in numerous tumors. The relationship of DC infiltration in the tumor microenvironment and prognosis was examined in patients with pancreatic adenocarcinoma. Methods. Forty-seven pancreatectomy specimens with a diagnosis of pancreatic adenocarcinoma were identified retrospectively and analyzed with the dendritic cell markers S-100 and CD1a. Patient survival was correlated with these markers and with p53, CD3, CD20, CD68, Ki-67. Results. Significant numbers (>3 per high-powered field) of tumor-associated S100+ or CD1a+ cells were found in only 2/47 patients (4%). When present, dendritic cells were located outside the margin of the tumor. CD3, CD68, and CD20 positive cells were rare or absent in 96%, 92%, and 93% of the specimens. A correlation with survival and numbers of immune cells could not be made secondary to their rarity. The median survival was 18.9 months. No other indices measured correlated with survival. Conclusions. In patients with pancreatic adenocarcinoma, there is a paucity of immune cells within the tumor. (Surgery 2002;131:135-8.)

Section snippets

Patient selection

A computerized search of operative reports at the University of Pittsburgh Medical Center from January 1990 to 1997 revealed 49 patients who had curative pancreatic resection for adenocarcinoma (48 Whipple specimens and 1 distalpancreatectomy). Of these, 2 were lost to follow-up. Follow-up was obtained through tumor registry, death certificates, and office records.

Histopathology

The 47 specimens were fixed in 10% neutral buffered formalin solution, routinely processed, and embedded with paraffin. Routine

Statistical method

We applied the Fisher exact test to categorical variables to determine whether associations exist among independent variables. We also used analysis of variance to evaluate whether distributions of continuous variables, tumor size, and Ki-67, differed significantly across levels of categorical variables. After analyzing the association among independent variables, we used the Cox proportional hazards model to assess the impact of independent variables on patient survival.

Patients

Of the 47 patients, 37 died during the follow-up period. Ten patients were right-censored. The median time to death was 13.4 months in the 37 patients known to have died, and the minimum and maximum times were 2.7 and 160.8 months, respectively. Among the 10 patients who were right-censored, the mean and median length of follow-up was 32.7 ± 15.9 months and 29.0 months, respectively. Based on Kaplan-Meier estimation of the survival function, median overall survival was estimated as 18.9 months

Discussion

Several previous studies have correlated intratumoral DC infiltrate and survival. We had hoped to demonstrate this effect in patients with pancreatic cancer, but we found only rare instances of significant DC infiltrate. Compared with other series, we had to devise a substantially more sensitive grading system. CD1a stains Langerhans' DC and is more specific (but less sensitive) than S100, which accounts for the greater number of S100+ cells. With these DC markers (S100, CD1a), significant

References (17)

There are more references available in the full text version of this article.

Cited by (77)

  • Immunotherapy for osteosarcoma: Fundamental mechanism, rationale, and recent breakthroughs

    2021, Cancer Letters
    Citation Excerpt :

    Fig. 2 shows the main process of generating ex vivo DC vaccines. The DC is essentially a professional antigen-presenting cell, accounting for only 0.3% of the entire cell population in the blood, which causes the proliferation of CTLs, and Lotze et al. reported that DC numbers were correlated with patient survival [6,41]. DC-based vaccines are the most common vaccination approaches in pediatric sarcomas [36], and the patients receiving the DC vaccine showed extended 5-year survival, from 31% to 43%, compared to the patients in the control arm.

  • Challenges and Opportunities for Pancreatic Cancer Immunotherapy

    2020, Cancer Cell
    Citation Excerpt :

    In KC mice, PanIN lesions are infiltrated by immunosuppressive tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Treg) (Clark et al., 2007). In KPC mice, type I conventional dendritic cells (cDC1) important for Teffector priming become progressively decreased and dysregulated as PanINs evolve to invasive tumors (Hegde et al., 2020; Lin et al., 2020), correlating with low levels of infiltrating dendritic cells (DCs) in human PDA samples (Dallal et al., 2002; Hiraoka et al., 2011). mKRAS drives tumor-intrinsic granulocyte macrophage colony-stimulating factor (GM-CSF) and chemokine C-X-C motif ligand 1 (CXCL1) expression, promoting TME MDSC infiltration (Bayne et al., 2012; Pylayeva-Gupta et al., 2012) and T cell exclusion (Li et al., 2018).

  • Pancreatic Cancer UK Grand Challenge: Developments and challenges for effective CAR T cell therapy for pancreatic ductal adenocarcinoma

    2020, Pancreatology
    Citation Excerpt :

    Similarly to MDSCs, Tregs bind to IL-2 and sequester it, reducing its availability and thus the proliferation of effector T cells [102]. Dendritic cells (DCs), which are cells of myeloid origin, are antigen presenting cells that are reported to be rare in PDAC tumors [103]. Effective antigen presentation by these cells is essential for normal anti-tumor T cell function.

  • Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer

    2020, Cancer Cell
    Citation Excerpt :

    Work from other groups have shown that TREGS also play an important role in sustaining pancreatic tumorigenesis (Zhang et al., 2014), although we did not observe this to be prominent in our study. Human PDAC patients have low numbers of DCs that become rarer with tumor progression (Dallal et al., 2002; Hiraoka et al., 2011). Such an absence or dysfunction of DCs can magnify unproductive TH cell responses (Furuhashi et al., 2012; Ibrahim et al., 2012; Ochi et al., 2012).

  • From tumor microenvironment communicants to biomarker discovery: Selectively packaged extracellular vesicular cargoes in pancreatic cancer

    2020, Cytokine and Growth Factor Reviews
    Citation Excerpt :

    Further, there are relatively low numbers of infiltrating CD4+ and CD8+ T cells [5]. Finally, the PDAC TME also demonstrates paucity of dendritic (DC) and natural killer (NK) cells[6,7]. This review focuses on the present understanding of EV cargos as cell-to-cell communicants, their ability to influence biology in remote organs evidenced by their presence in the circulation (further discussed in section 3 of this review and depicted in Fig. 2), and their potential value as diagnostic and prognostic biomarkers.

  • Interventional therapy combined with radiotherapy for pancreatic carcinoma

    2020, Integrative Pancreatic Intervention Therapy: A Holistic Approach
View all citing articles on Scopus
*

Supported in part by a grant from the National Institute of Health PO1-CA73743 and the Society of University Surgeons Fellowship grant.

**

Reprint requests: Ramsey M. Dallal, MD, 200 Lothrop St, 677 Scaife Hall, Department of Surgery, Pittsburgh, PA 15261.

View full text