MHC class II expression in pancreatic tumors: a link to intratumoral inflammation
Major histocompatibility complex class II antigens (MHC class II) are constitutively expressed by professional antigen presenting cells and present antigenic peptides to specific CD4+ T lymphocytes. MHC class II expression, however, can also be induced on epithelial cells and in a variety of solid tumors. We tested MHC class II expression on tissue samples derived from patients with pancreatic ductal adenocarcinoma (PDAC) and pancreatic endocrine tumors (PET). Immunohistochemistry revealed MHC class II expression in 86 of 112 (76.8%) PDAC samples and in 30 of 43 (70.0%) PET samples. In PDAC and PET, MHC class II expression correlated significantly with severity and activity of intratumoral inflammation, as well as with the infiltration of CD4+ T lymphocytes. High MHC class II expression significantly correlated with a better histological grade of differentiation in PDAC. In vitro MHC class II expression could be induced on PDAC tumor cell lines by interferon-γ. These cells were then able to present the staphylococci enterotoxin B superantigen to T lymphocytes, which resulted in T cell proliferation. Our findings suggest that MHC class II expression on pancreatic tumor cells is induced by the intratumoral inflammatory reaction in pancreatic tumors.
KeywordsPancreatic cancer Pancreatic endocrine tumor MHC class II Intratumoral inflammation T cell proliferation
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive neoplasm, ranking fourth in cancer-related deaths in western countries . Tumors are significantly influenced by the cross-talk among the tumor cells and by their microenvironment, particularly the tissue-resident cells such as fibroblasts, or the tumor-infiltrating lymphocytes and the inflammatory cells . The intratumoral inflammation in the PDAC microenvironment is often distinct, and multiple interactions between tumor cells and cells of the immune system have been previously described, but the impact on tumor progression is not yet understood [3, 4, 5]. Systemically increased C-reactive protein concentrations, a marker for an active inflammatory constitution, correlates with shorter survival of PDAC patients . Moreover, an intensive interplay between pancreatic tumor cells and inflammatory cells has been reported . Cytokines released by tumor infiltrating lymphocytes were shown to enhance the invasion of pancreatic cancer cells [4, 7], while neutrophil-derived lipocalin provided an anti-tumoral and anti-metastatic effect in PDAC .
Key findings include the fact that PDAC cells are specifically recognized by autologous T lymphocytes  and that chemokines or their receptors, such as CXCL14 or CXCL16 and its corresponding receptor CXCR6, are found in PDAC that could mediate interactions with inflammatory cells in particular [10, 11, 12, 13]. Moreover, major histocompatibility antigen (MHC) class I and class II are found on a variety of tumor cells, including pancreatic adenocarcinoma cells , and it has been assumed that they provide the immunologic recognition structure of the tumor by presenting either an “altered self” or a “non-self antigen” to T lymphocytes [15, 16].
The constitutive MHC class II expression is restricted to professional antigen presenting cells, such as dendritic cells, monocytes, and B lymphocytes. MHC class II expression, however, can be induced in non-neoplastic tissue under inflammatory conditions, particularly on epithelial cells like keratinocytes or intestinal mucosa [17, 18]. MHC class II antigens are also expressed by human malignancies, e.g. in Ewing sarcoma , malignant melanoma , renal cell carcinoma , colon carcinoma , breast cancer , and squamous cell carcinoma of the larynx [22, 23]. MHC class II expression has been associated with better tumor differentiation and a better prognosis, e.g. in colon, breast and larynx carcinoma [21, 22, 23, 24].
Expression of MHC class II in PDAC tissue was indicated by two preliminary studies, comprising only a small number of patients [14, 25], on isolated cells of primary PDAC , and on pancreatic adenocarcinoma cell lines . These first studies reported that approximately 30% of PDAC tissues revealed MHC class II positivity [14, 25]. In the present study, we examined MHC class II expression in a large series of 112 PDAC patients and for comparison additionally of 43 patients with PET and assessed the correlation with clinical and pathological parameters focussing the intratumoral inflammation. To gain insight into the functional role of MHC class II expression in tumors, we tested whether pancreatic cancer cells that were induced to express MHC class II molecules were able to activate T lymphocytes using staphylococcus enterotoxin B as a model superantigen . We found a strong correlation between MHC class II expression by pancreatic tumor cells and the intratumoral inflammatory reaction, particularly with respect to the infiltration of CD4+ T lymphocytes. Moreover, the in vitro data provided evidence for the propensity of MHC class II positive tumor cells to induce the proliferation of T lymphocytes. Taken together, our data suggest that the proinflammatory microenvironment induces the MHC class II expression on the tumor, and the tumor cell, in turn, might participate in a localized immune reaction.
Material and methods
PDAC tumor tissue samples were obtained from 112 patients (46 female, 66 male; age range, 39–85 years; mean, 64.9 years; median, 66.0 years). In 84 patients the tumors were located in the pancreatic head, 7 in the body, 13 in the body and tail, and 8 were in the tail. The tissue specimens were formalin-fixed and paraffin-embedded.
Clinical and pathological parameters of PDAC patients
Patients (n = 112)
Gender (F/M) (n = 112)
39–85 (mean, 64.9; median, 66.0)
Location of tumor
Body and tail, 13
Survival (n = 104 patients)
Death of disease, 61 patients; 25–1,187 days (mean, 427; median, 347)
Alive, 37 patients; 15–1,044 days (mean, 551; median, 663)
Non-cancer-related death, 6 patients
Clinical and pathological parameters of PET patients
Patients (n = 43)
Gender (F/M) (n = 43)
13–85 (mean, 56.0; median, 60.0)
Location of tumor
Body and tail, 5
Diagnosis (WHO 2004)
Well-differentiated endocrine tumor, 6
Well-differentiated endocrine tumor of uncertain behaviour, 8
Well-differentiated endocrine carcinoma, 25
Poorly differentiated endocrine carcinoma, 4
Diagnosis (WHO 2010)
Neuroendocrine tumor, 35
Neuroendocrine carcinoma, 8
Chromogranin A, 43
Immunohistochemical hormone expression
Insulin, 12 (27.9% of 43 cases)
Gastrin, 10 (23.2% of 43 cases)
Glucagon, 3 (7.0% of 43 cases)
Pancreatic polypeptide, 3 (7.0% of 43 cases)
Somatostatin, 3 (7.0% of 43 cases)
Serotonin, 1 (2.3% of 43 cases)
Clinically determined functional activity
Insulinoma, 11 (25.6% of 43 cases)
Gastrinoma, 4 (9.3% of 43 cases)
Glucagonoma, 1 (2.3% of 43 cases)
Survival (n = 37 patients)
Death of disease, 8 patients; 1–1,258 days (mean, 477; median, 260)
Alive, 29 patients; 47–4,980 days (mean, 1,480; median, 1,466)
The study was approved by the Ethics Committee of the University of Heidelberg and written informed consent was obtained from the patients.
Paraffin-embedded tissue sections (4 μm) were used for the immunohistochemical analyses. Immunostaining was performed as previously described , using the avidin–biotin complex method. Prior to antibody incubation, heat pre-treatment in an antigen retrieval solution (DAKO; pH 9.0) was performed. Primary antibodies included a mouse monoclonal antibody to MHC class II (Abcam, Cambridge, UK; diluted 1:250) and a mouse monoclonal antibody to CD4 (Novocastra, Newcastle, UK; diluted 1:10). MHC class II staining was performed on tissue microarrays from 112 PDAC samples, 43 PET samples and ten normal pancreas samples. To validate these immunohistochemical results obtained from the microarrays, 16 and 26 of the cases were additionally stained for MHC class II and CD4, respectively, using whole tissue tumor sections, revealing comparable results.
Scoring of inflammation, CD4+ T lymphocyte infiltration and MHC class II expression
The severity of the inflammation was evaluated microscopically on whole tumor sections, using a previously reported scoring system . Briefly, the severity was determined as absent (score, 0), mild (score, 1), moderate (score, 2) or severe (score, 3), depending on the accumulation of inflammatory cells (lymphocytes, plasma cells, macrophages) and the formation of lymph follicles. The activity of inflammation was semiquantitatively scored as absent (score, 0), mild (score, 1) or moderate to severe (score, 2), depending on the density of neutrophil granulocytes.
The immunohistochemical MHC class II expression (distribution) of the tumor cells was determined semiquantitatively as score, 0 for 0%; score, 1 for 1–5%; score, 2 for 5–25%; score, 3 for 25–50%; score, 4 for 50–75% and score, 5 for 75–100% positive tumor cells according to a previously reported scale for the immunohistochemical evaluation of the expression of MHC molecules [15, 34, 35]. This scoring system includes also a semiquantification of the staining intensity, as grouped in no staining (score, 0), weak staining intensity (score, 1), moderate staining intensity (score, 2) or strong staining intensity (score, 3). According to Berghuis et al. we used an immunoreactivity score (in accordance to the Allred-Score), in which the summation of both scores was composed .
CD4+ T lymphocytes have been described to interact with MHC class II molecules . To test the correlation between the MHC class II expression on PDAC and PET and the infiltration of CD4+ lymphocytes, the CD4+ T lymphocytes were counted in ten representative high power fields (HPF) of each case in 112 PDAC and in 21 PET cases.
TMA specimen and the corresponding whole tissue sections were compared, and the ratio between the mean number of CD4+ infiltrating cells in sections with high MHC class II expression and those without any expression was calculated. The ratio (CD4+ lymphocytes in high MHC class II expressing tumors/CD4+ lymphocytes in non-MHC class II expressing tumors) was 4.0 in whole tissue sections and 3.8 in TMA; thus a valid tool for the quantification of CD4+ lymphocytes was generated. Next, we compared the expression pattern and intensity of MHC class II with the number of infiltrating CD4+ T lymphocytes. Furthermore, we correlated the infiltrate of CD4+ lymphocytes in tumors with MHC class II expression (irrespective of the quantity of positively staining cells) versus tumors without any expression. Moreover, we selected 13 cases without MHC class II expression and 13 cases with notably high MHC class II expression (more than 75% positive cells, moderate to strong staining intensity) to compare the infiltration of CD4+ T lymphocytes.
Cytofluorometry and induction of MHC class II expression on pancreatic cancer cell lines
The pancreatic tumor cell lines Capan-1, MiaPaca-2, BxPC-3, Panc-1, SU8686, AspC1, (ATCC, Rockville, MD, USA), T3M4 and Colo-357 (R.S. Metzgar Duke University, Durham, NC, USA) were cultivated in RPMI 1640, supplemented with 10 % fetal calf serum, 1% l-glutamine and 1% penicillin/streptomycin (all obtained from Invitrogen, Karlsruhe, Germany). For induction of MHC class II expression, the cells were seeded into 6-well plates (NUNC, Roskilde, Denmark; 1 × 105/ml), and cultivated with interferon-γ (Serotec, Düsseldorf, Germany; 100 U/ml) for 24 and 48 h, respectively. Next, the cells were washed, removed from the plates by treatment with EDTA/Trypsin (Invitrogen) and suspended in phosphate-buffered saline (PBS) containing 1% bovine serum albumin and 0.1% sodium azide. To detect MHC class II surface expression, 5 μl PE-labelled antibody (anti-HLA-DR-DQ-DP; Biozol, Eching, Germany) was added. Mouse IgG-PE (BD Pharmingen, Heidelberg, Germany) was used as an isotype control. After 30 min, the cells were washed, resuspended in 1% paraformaldehyde in PBS and antibody binding was measured by FACScalibur® (Becton and Dickinson, Heidelberg, Germany).
MHC class II-mediated superantigen presentation of pancreatic tumor cells to CD4+ T lymphocytes
The pancreatic cell lines Colo-357 and SU8686 were cultivated in the presence of interferon-γ to induce MHC class II expression as described above and then irradiated for 14 min (60 Gy) to prevent their proliferation. T lymphocytes were isolated from the peripheral blood of a healthy donor according to established methods. In brief, heparinized blood was layered onto PolymorphPrep® (Axis-Shield, Oslo, Norway), and the mononuclear cell fraction was recovered according to the protocol of the supplier. T lymphocytes were separated from the mononuclear cell fraction by magnetic beads separation using anti-CD3 beads (MACS Miltenyi Biotec, Bergisch Gladbach, Germany). The T lymphocytes were adjusted to 1 × 106/ml in RPMI supplemented with 10% fetal calf serum, 1% HEPES, 1% l-glutamine, and 1% penicillin/streptomycin (all obtained from Invitrogen) and 100 μl were placed into a round-bottom 96-well culture plate. The irradiated pancreatic cells (100 μl in the concentrations indicated in the respective experiment) were added with or without staphylococci enterotoxin B (SEB; 2 ng/well; Sigma-Aldrich, Munich, Germany). After 48 h, 3H-thymindine was added (1 μCi/well) for another 24 h and incorporation into the cells of radioactivity was measured. For comparison, pancreatic cancer cells without previous interferon-γ stimulation were used, as were T lymphocytes alone and pancreatic cancer cells alone with or without SEB. The T lymphocyte proliferation was determined as mean value of five replicas, and the differences between groups were determined using ANOVA.
For statistical analysis of survival, the non-parametric logrank test was performed. Correlation of MHC class II expression with clinical and pathological parameters was performed using Spearman’s rho analysis. Correlation of MHC class II staining with the density of CD4+ T lymphocytes was calculated with the Spearman’s rho analysis and the Mann–Whitney U test, respectively. For the array analysis, the staining results were grouped as described above. Significance levels were defined as p < 0.05. The statistical analyses were carried out with the SPSS software version 18.0 for Windows (SPSS Inc., Chicago, USA). Graphs were made using OriginPro7.5 software (Additive Software, Friedrichsdorf, Germany).
Correlation of MHC class II expression with the severity and activity of intratumoral inflammatory reaction in PDAC and PET
Severity and activity of intratumoral inflammation in PDAC and PET
Number of cases
Severity of inflammation
Activity of inflammation
PDAC (n = 112)
Total: 112/112 (100.0%)
Total: 108/112 (96.4%)
Score 3: 20/112 (17.8%)
Score 2: 51/112 (45.5%)
Score 2: 80/112 (71.4%)
Score 1: 57/112 (50.9%)
Score 1: 12/112 (10.7%)
Score 0: 0/112
Score 0: 4 /112 (3.6%)
PET (n = 43)
Total: 32/43 (74.4%)
Total: 22/32 (68.8%)
Score 3: 0/43
Score 2: 2/32 (6.3%)
Score 2: 5/43 (11.6%)
Score 1: 20/32 (62.5%)
Score 1: 27/43 (62.8%)
Score 0: 11/43 (25.6%)
Score 0: 10/32 (31.2%)
MHC class II expression in PDAC and PET with percentage of immunoreactive tumor cells
Number of cases
MHC class II expression
MHC class II intensity
PDAC (n = 112)
Total, 86/112 (76.8%)
Strong, 9/86 (10.5%)
0, 26/112 (23.2%)
>75%, 19/86 (22.1%)
Moderate, 32/86 (37.2%)
2, 5/112 (4.5%)
50–75%, 12/86 (13.9%)
Weak, 45/86 (52.3%)
3, 5/112 (4.5%)
25–50%, 44/86 (51.2%)
4, 29/112 (25.9%)
5–25%, 5/86 (5.8%)
5, 22/112 (19.7%)
1–5%, 6/86 (7.0%)
6, 8/112 (7.1%)
7, 8/112 (7.1%)
8, 9/112 (8.0%)
PET (n = 43)
Total, 30/43 (70.0%)
Strong, 0/30 (0.0%)
0, 13/43 (30.0%)
>75%, 6/30 (20.0%)
Moderate, 13/30 (43.3%)
2, 8/43 (18.7%)
50–75%, 5/30 (16.7%)
Weak, 17/30 (56.7%)
3, 4/43 (9.3%)
25–50%, 16/30 (53.3%)
4, 1/43 (2.3%)
5–25%, 1/30 (3.3%)
5, 4/43 (9.3%)
1–5%, 2/30 (6.7%)
6, 8/43 (18.7%)
7, 5/43 (11.6%)
8, 0/43 (0%)
MHC class II antigen expression on PDAC cancer cells showed a significant positive correlation with the severity of the inflammation (p = 0.001) as well as with the activity of the inflammation (p = 0.007). Furthermore, the MHC class II staining intensity correlated positively with the severity (p < 0.001) and the activity of the inflammation (p = 0.002).
Using the immunoreactivity score, a positive correlation between severity (p < 0.001) and activity (p = 0.001) and the MHC class II expression was seen. Again, PET yielded essentially similar results, a positive correlation of MHC class II antigen expression with the severity of the intratumoral inflammation (p < 0.001) and with the activity of the intratumoral inflammation (p < 0.001) was seen; MHC class II staining intensity correlated with the severity (p = 0.003) and the activity of the intratumoral inflammation (p < 0.001). The immunoreactivity score revealed a significant positive correlation between the MHC class II expression and the severity (p < 0.001) and the activity (p < 0.001).
Correlation of MHC class II expression in PDAC and PET with clinical and pathological parameters
The expression of MHC class II in PDAC (distribution, intensity and the immunoreactivity score) showed a significantly negative correlation with the tumor grade (p = 0.001), but not with the local tumor stage (pT), the presence of regional lymph node metastases (pN), distant metastases (pM) or patient gender. No correlation between the survival of the patients and MHC class II expression (p = 0.70) or intensity (p = 0.88) was found. In PET, the distribution of the MHC class II (p = 0.042) and the calculated immunoreactivity score (p = 0.027) significantly correlated with the local tumor stage (pT).
MHC class II expression parameters (distribution, intensity and the immunoreactivity score) revealed no significant correlation between the diagnostic tumor classification (WHO 2004 and 2010 and ENETS), histopathological grading, hormone expression of insulin or glucagon, functional activity, presence of a hereditary syndrome (MEN 1 syndrome), or gender of the patients. The endocrine carcinomas among the collective showed no correlation between the MHC class II expression and the presence or absence of regional lymph node (pN) or distant organ metastases (pM). No correlation with patient survival could be demonstrated with respect to distribution (p = 0.91) or intensity (p = 0.40).
MHC class II-positive PDAC tumor cells present superantigen to T lymphocytes and mediate T cell activation
Induction of MHC class II expression on ductal pancreatic tumor cell lines (48 h), measured as the percent of cells expressing MHC class II
MHC class II expression
Isotype (IgG) control
Culture without interferon-γ
Following culture with interferon-γ
Culture without interferon-γ
Following culture with interferon-γ
In the present study, we focussed on rather specialized interaction molecules, the MHC class II complex (HLA-DR, DP, DQ) because as specialized recognition molecules they could provide a link between the local inflammation and the specific immune response. Under physiological conditions, constitutive expression of MHC class II molecules is restricted to professional antigen presenting cells, including dendritic cells, monocytes and B lymphocytes. MHC class II molecules bind processed antigenic peptides and present them to the antigen-specific T cell receptors on CD4+ T lymphocytes. The ensuing antigen-specific T cell activation is dependent on appropriate co-stimulatory signals and can be modified by the cytokines within the microenvironment [38, 39]. MHC class II expression, however, is not limited to antigen presenting cells. Under inflammatory conditions, polymorphonuclear neutrophils  and epithelial cells  acquire MHC class II molecules. Moreover, a variety of tumor cells express MHC class II [21, 22, 23, 24]. The data for pancreatic ductal adenocarcinoma are rather limited. In two studies MHC class II expression in three out of eight patients  and in 11 out of 37 patients  was described. According to another study, expression of MHC class II could not be demonstrated by cytofluorometry in untreated, primary PDAC cells of 19 patients , while others found MHC class II on cultured PDAC lines  that could be induced by interferon-γ [14, 25]. In our series, MHC class II expression was detected in the majority of PDAC (76.8%) and of PET (70.0%). MHC class II expression correlated positively with the severity and the activity of the inflammatory reaction, and notably, with the infiltration of CD4+ T lymphocytes. Since the latter produce interferon-γ, the major effector cytokine for induction of MHC class II antigens in professional and non-professional antigen presenting cells , these data suggest that the infiltrating CD4+ T lymphocytes induce the MHC class II expression on the tumor cells. The fact that infiltrating T lymphocytes or PDAC tissue-derived tumor-reactive T lymphocytes release interferon-γ has been shown before [3, 42, 43]; moreover, we found that interferon-γ induced surface expression of MHC class II antigen on pancreatic tumor cell lines. Additionally, stained normal pancreas tissue revealed no MHC class II expression, reflecting the MHC class II expression as an effect induced by the inflammatory microenvironment in the tumor.
The fact that the cell lines varied with regard to MHC class II expression could reflect their differentiation status: well or moderately differentiated cell lines such as Capan-1, Su8686 T3M4 or AsPC1 acquired more MHC class II after interferon-γ stimulation compared to the poorly differentiated cell lines Panc-1 or Colo-357. These data are in accordance to our histological findings, in which high levels of MHC class II expression coincided with a better histological differentiation grade. De-differentiation of the tumors may probably cause a loss of MHC class II antigen expression of tumor cells. In our study, the presence or absence of lymph node or distant metastases did not correlate with MHC class II expression in the PDAC collective, nor did the pT stage, the latter obviously due to the fact that 110 patients revealed a pT3 status. In PET, pT stage correlated significantly with the expression of MHC class II expression by endocrine tumor cells.
MHC class II expression did not correlate with lymph node or organ metastases, corresponding to the findings of Monti et al., who tested pancreatic cancer cell lines either cultivated from the primary tumors or from metastases revealing no differences of MHC class II expression .
So far, the functional role of MHC class II molecules on tissue cells is poorly understood. Except for the special situation in the thymus, in which thymus epithelial cells present self-antigens and thereby contribute to the shaping of the T cell repertoire, only in vitro data are available showing that MHC class II on tissue cells such as keratinocytes , tubular epithelial cells  or synovial fibroblasts  can present superantigen to T cells, thereby inducing their proliferation. The special situation of superantigens, such as, the staphylococcus enterotoxin (SE) B used as reliable model superantigen in our study, is that they bind to the non-variable region of the MHC class II molecule without prior processing and are recognised by a large number of CD4+ T lymphocytes in a MHC class II-dependent but unrestricted and antigen-unspecific manner. Binding results in the activation of T cells, apparent as proliferation . Under our experimental conditions, we found that pancreatic tumor cell lines induced to express MHC class II antigens were able to trigger T cell proliferation when SEB was present.
The role of activated T cells, particularly that of CD4+ T lymphocytes, is currently under intense investigation and pro- or antitumorigenic functions have been described, depending on the cytokine environment [49, 50, 51]. Pancreatic tumor cells are specifically recognized by autologous T lymphocytes . Based on these observations and our results, MHC class II antigens on pancreatic tumor cells might serve as a means to present tumor-associated antigens. According to the classical dogma, MHC class II molecules present processed exogenous antigens as opposed to self-antigens that are presented by MHC class I. This strict segregation, however, no longer holds true, and multiple alternative antigen-presenting pathways involving MHC class II antigens have been described . In that, MHC class II expression on pancreatic tumor cells could participate in the CD4+ T lymphocyte-mediated arrest of carcinogenesis. However, no correlation between MHC class II expression and patient survival was seen in our study, which is quite in contrast to data on patients with colorectal cancer, in which MHC class II expression correlated with a better survival . The generally dismal prognosis of PDAC patients with a 5-year survival rate of less than 5% assembling all components like aggressive and invasive tumor growth, early metastasis and resistance to radiation and chemotherapy , overbalances probably the effects of the MHC class II-mediated immune reaction and of the surrounding inflammatory infiltrate in PDAC. For PET, correlations with MHC class II molecules and survival should be performed in a larger series including longer follow-up periods to obtain reliable results. Nevertheless, the inflammatory infiltrate, influencing the tumor cell growth, tumor cell migration or tumor neoangiogenesis [10, 12, 54], might also be an important factor in PET biology. As previously shown for malignant melanoma, even scarce inflammatory infiltrates may significantly affect the tumor biology and the resulting prognosis of the patients .
The question arises whether the expression of MHC class II antigens on tumor cells might have some benefit for patients with PDAC or PET. A major problem in the host defence and by analogy of immunologic-based therapies is the “tumor-immune-escape” , which—at least in part—is due to the downregulation of recognition structures on the tumor cells, including MHC molecules . In this context, pancreatic ductal adenocarcinomas  as well as pancreatic endocrine tumor cells , are characterized to reveal a loss of MHC class I molecules, probably to escape a CD8+ T cell-mediated cytotoxic reaction. A direct relationship between the expression profiles of MHC class I and class II molecules could not be demonstrated in a study for PDAC, though both molecules are inducible by interferon-γ . Consequently, in various clinical trials, e.g. on malignant melanoma, interferon was applied to induce MHC class I and MHC class II molecules and as consequence levels of melanoma-specific CD4+ T lymphocytes increased [58, 59]. Since MHC class II can be induced also on pancreatic cancer cells, an interferon-γ-based therapy is worth considering, especially in better differentiated cancers. On the other hand, a note of caution is imperative: MHC class molecules can also induce antigen-specific anergy of T lymphocytes, e.g. when co-stimulatory signals on the target cells are missing . In conclusion, our findings suggest that MHC class II expression on pancreatic tumor cells is induced by the intratumoral inflammatory reaction in pancreatic tumors and might play an important role in the interaction of the inflammatory cells with pancreatic tumors.
We thank Prof. Dr. Ulrich Abel, Department of Medical Biometry, University of Heidelberg for the professional evaluation of the biostatistics. We thank Mrs. Birgit Prior, Institute for Immunology, University of Heidelberg and Mrs. Sarah Messnard, Institute of Pathology, University of Heidelberg for their excellent technical support.
Conflict of interest statement
None of the authors declare a conflict of interest.
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