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PubMed2006

Acute renal failure caused by renal infiltration by hematolymphoid malignancy.

Renal involvement by a malignant infiltrative process is often suspected in patients with bilaterally enlarged kidneys and concurrent malignancies. Acute renal failure (ARF) can rarely occur secondary to such an infiltrative process. We present 2 cases in which ARF is attributable to malignant hematolymphoid infiltration. The first case involves diffuse, bilateral involvement of the kidneys by non-Hodgkin's lymphoma. The patient's renal function improved dramatically after the initiation of chemotherapy, clearly linking the development of ARF to the malignant process. In the second case, infiltration of the kidneys by plasma cell leukemia resulted in dialysis dependence. To our knowledge, this represents the first reported case of ARF attributable to documented renal infiltration by plasma cell leukemia. A review of the potential causes of renal failure in hematolymphoid malignancy, focusing on the direct impact of the infiltrative process and on the spectrum of renal disease in plasma cell dyscrasia, is presented.

Acute Kidney Injury↗

PubMed2003

3-Aminobenzamide reduces brain infarction and neutrophil infiltration after transient focal cerebral ischemia in mice.

Poly(ADP-ribose) polymerase (PARP) was shown to be detrimental in cerebral ischemia but the mechanisms whereby PARP is deleterious have yet to be determined. They may include a role in neutrophil infiltration known to aggravate ischemic damage. In this context, we investigated the effect of 3-aminobenzamide (3-AB), a PARP inhibitor, on brain damage and neutrophil infiltration after transient focal cerebral ischemia in mice. Ischemia was induced in male Swiss mice, anaesthetized with chloral hydrate (400 mg/kg, i.p.), by a 15-min-occlusion of the left middle cerebral artery using an intraluminal suture. Treatments with 3-AB were first administered intraperitoneally 15 min before reperfusion and endpoints measured at 24 h. Among the range of dosages studied (20-320 mg/kg), 40 mg/kg gave the maximal neuroprotection with a 30% decrease in the infarct volume and tended to improve the neurological score evaluated by a grip test. The same dosage was, however, devoid of effect when injection was delayed 2 or 6 h after reperfusion. Myeloperoxidase (MPO) activity used as an index of neutrophil infiltration showed that infiltration peaked 48 h after reperfusion in our model. At this time point, 3-AB (40 mg/kg given 15 min before reperfusion) markedly reduced the neutrophil infiltration, as evidenced by a 72%-decrease in MPO activity, and was still neuroprotective. Our results confirm that 3-AB reduces brain damage. Moreover, for the first time, a quantitative study shows that 3-AB decreases neutrophil infiltration elicited by cerebral ischemia.

Animals↗

PubMed2002

Increased expression of activation markers in renal cell carcinoma infiltrating lymphocytes.

PURPOSE: As manifested by the presence of immune competent cells, failure to control the progression of renal cell carcinoma by a local immune response attests to impaired local cell mediated immunity. To test this hypothesis we compared the expression of T-cell activation markers in renal cell carcinoma infiltrating lymphocytes with the expression of activation markers of peripheral blood lymphocytes in the same patients. MATERIALS AND METHODS: Tumor infiltrating lymphocytes were harvested from a patient with renal cell carcinoma undergoing radical nephrectomy. Peripheral blood was obtained before surgery. Tumor infiltrating and peripheral blood lymphocytes were incubated with monoclonal antibodies defining specific differentiation and activation markers on the cell surface, and analyzed by flow cytometry. Cell subsets are expressed as a fraction of the total number of mononuclear cells. RESULTS: The T-cell subset level was significantly higher in peripheral blood than in renal cell carcinoma tissue of the same patient. However, the level of activated T-cell subset expressing HLA-DR was significantly higher in renal cell carcinoma tissue than in peripheral blood. The levels of interleukin-2 receptor and transferrin receptors expressing T-cell subsets were also significantly higher in carcinoma tissue than in peripheral blood. Natural killer cells were found in significantly higher proportions in renal cell carcinoma than in peripheral blood. CONCLUSIONS: These results point to significant activation of T, B and natural killer tumor infiltrating lymphocytes. The inability of tumor infiltrating lymphocytes to mount an effective immune response to renal cell carcinoma may be secondary to the presence of suppressive factors in the tumor that prevent tumor infiltrating lymphocytes from transforming into effector cells. These factors may be particularly valuable for the further study of renal cell carcinoma-host interactivity.

Aged↗

PubMed1993

Interferon-alpha primed tumor-infiltrating lymphocytes combined with interleukin-2 and interferon-alpha as therapy for metastatic renal cell carcinoma.

Murine models demonstrate therapeutic synergy for the combination of interleukin-2, interferon-alpha and tumor-infiltrating lymphocytes. We treated 11 patients with metastatic renal cell carcinoma with a novel regimen consisting of in vivo primed tumor-infiltrating lymphocytes, interferon-alpha and interleukin-2. Patients received interferon-alpha before radical nephrectomy; in vivo primed tumor-infiltrating lymphocytes were isolated and expanded in vitro. Low dose continuous infusion interleukin-2 at a dose of 2 x 10(6) units per m.2 per day was administered for 96 hours during each treatment week and interferon-alpha was administered as a subcutaneous injection at a dose of 6 x 10(6) units per m.2 per day on days 1 and 4 of the interleukin-2 infusion. No therapy was given during the last 3 days of a treatment week. One course of therapy consisted of 3 weeks of therapy followed by 3 weeks of rest. Patients were treated until maximal response, disease progression or dose limiting toxicity. A maximum of 6 courses of therapy were administered. Eleven patients underwent interferon-alpha priming and subsequent radical nephrectomy. In vivo primed tumor-infiltrating lymphocytes were successfully expanded in all 11 patients with an expansion index of greater than 170. In vivo primed tumor-infiltrating lymphocytes maintained their lytic activity for greater than 5 to 8 weeks in culture as demonstrated in the 4-hour 51chromium release assay. Ten patients underwent multimodality biological therapy and 3 (30%, 95% confidence interval 6 to 65%) have achieved complete response (2 clinical and 1 surgical) with durations of 24+, 23+ and 5+ months. Patients with stable disease received no additional therapy. No deaths and no grade 4 toxicities occurred. Immunotherapy using a combination of interferon-alpha primed tumor-infiltrating lymphocytes, low dose continuous infusion interleukin-2 and interferon-alpha can induce significant and durable antitumor responses in some patients with advanced renal cell carcinoma.

Adult↗

PubMed2000

The histologic value of adnexal (eccrine gland and follicle) infiltration in mycosis fungoides.

BACKGROUND: To verify the incidence and the possible diagnostic use of detecting adnexotropism in mycosis fungoides (MF). METHODS: We reviewed the frequency and the intensity of the eccrine and follicular infiltration in 104 biopsy specimens from indisputable cases of MF and in a control group of 20 biopsy specimens of spongiotic dermatitis. Syringohyperplasia and follicular mucinosis were also evaluated. RESULTS: A prominent eccrine infiltration was noted in 32 of 104 specimens (30%). Marked acrosyringial and ductal eccrine hyperplasia was present in 5 specimens (5%). In 13 of the 32 specimens with prominent eccrine infiltration (40%), epidermotropism was slight or less evident than syringotropism. Follicular structures were visible in 59 specimens and significantly infiltrated in 57%. Follicular mucinosis was found in 5 (8.4%). In the control group of spongiotic dermatitis, a significant eccrine and follicular infiltration was found only in case (5%). CONCLUSIONS: Adnexal (eccrine gland and follicle) infiltration may be a useful diagnostic tool in MF, particularly in those in which epidermotropism is slight.

Eccrine Glands↗

PubMed2002

Intrasinusoidal bone marrow infiltration: a common growth pattern for different lymphoma subtypes.

We report a retrospective immunohistochemical study on bone marrow biopsies of 43 patients with different types of lymphomas showing unusual intrasinusoidal infiltration. Most of these patients presented with splenomegaly (74.4%) and peripheral lymphocytosis (83%). In 20/43 patients, lymphoid infiltrates were not detectable on haematoxylin-eosin sections. After immunohistochemistry on bone marrow biopsies and blood and bone marrow smear examinations, the following diagnoses were made: splenic marginal zone lymphoma with villous lymphocytes (SLVL) in 24 patients, large granular lymphocyte (LGL) leukaemia in 14 patients, hepatosplenic T-cell lymphoma in two patients, anaplastic large cell lymphoma in two patients and intravascular large B-cell lymphoma in one patient. In the presence of intrasinusoidal infiltrates of small lymphocytes, a B-cell phenotype (CD20+, CD76/DBA44+/-) was associated with splenic marginal zone lymphoma whereas intrasinusoidal CD3/CD45RA-positive T-cell infiltrates were strongly suggestive of LGL leukaemia. Intrasinusoidal bone marrow infiltration appears to be a common feature of distinct lymphoma subtypes. Immunohistochemical analysis is essential to detect intrasinusoidal medullary infiltrates (which may be minimal) and should be systematically performed in patients with splenomegaly and peripheral lymphocytosis.

Adolescent↗

PubMed1998

Infiltration patterns of short- and long-term cultured A-NK and T-LAK cells following adoptive immunotherapy.

Direct contact between lymphokine-activated killer (LAK) cells and tumour cells is believed to be imperative for initiating tumour cell lysis in vitro as well as in vivo. In order to optimize adoptive immunotherapy (AIT) it is therefore desirable to identify the LAK cell subtype, which ensures maximal infiltration of tumours as well as a substantial cytotoxic reactivity. In this report we have compared short- and long-term cultured murine adherent natural killer (A-NK) cells and mitogen-stimulated, lymphokine-activated T-killer (T-LAK) cells with respect to their proliferative potential, cytotoxicity, requirement for interleukin-2 (IL-2) and ability to infiltrate B16 pulmonary metastases following adoptive transfer. We found that short-term (5 days) cultured A-NK and T-LAK cells both showed a substantial accumulation of tumour tissues. However, A-NK cells gradually lost this ability during in vitro culture whereas T-LAK cells cultured for as long as 20 days retained their ability to infiltrate metastases as efficiently as their short-term cultured counterparts. Moreover, the low requirement of IL-2 by T-LAK cells to achieve maximal infiltration of tumours sharply contrasted with the excessive doses necessary to ensure maximal infiltration by A-NK cells. In conclusion, these data demonstrate that short-term cultured LAK cells of both NK- and T-cell origin are able to infiltrate B16 pulmonary metastases effectively. Importantly, the T cells retain this ability for a considerably longer time and require much less IL-2 support than do A-NK cells, making T-LAK cells attractive for AIT.

Animals↗

PubMed1997

Flow cytometric analysis of tumour-infiltrating lymphocytes in patients with renal cell carcinoma.

OBJECTIVE: To determine the immunophenotype of tumour-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) isolated from patients with renal cell carcinoma (RCC) and to analyse the correlations between the quantity of analysed cell subsets and the progression of the disease. PATIENTS AND METHODS: PBL and TIL samples were obtained from 23 patients with RCC at different stages of disease. The immunophenotype of PBL and TIL was measured, and the TNM stage, tumour size, cellular type, histological grade, lymphocytic infiltration and performance status assessed. RESULTS: The predominant mononuclear cells infiltrating the tumour, in all patients, were T lymphocytes (CD3+ median 66.9%, CD8+ median 34.6%, CD4+ median 26.7%). The cells possessing gamma/delta type T cell receptor accounted for a small fraction of the T cells in PBL and TIL (median 5.6% and 3.7%). Tumour-infiltrating T lymphocytes had a significantly higher percentage of cells expressing human leucocyte antigen (HLA) DR (median 30.9%) and CD25 (median 6.2%) antigens than the equivalent populations in peripheral blood from the same patient group (P < 0.001). The degree of T cell activation appeared to negatively correlate with the tumour stage (K = -0.3, P = 0.04). The percentage of natural killer (NK) cells among TIL (median 15.4%) did not reflect the value in PBL. The percentage of B cells in TIL was slightly lower than in PBL and accounted for 5.0% of cells. There was no relationship between the degree of lymphocytic infiltration and either tumour stage or grade but there appeared to be a positive correlation between the intensity of lymphocytic infiltration and the percentage of CD4+ cells in TIL (K = 0.5, P = 0.001). Moreover, the composition of TIL depended on tumour grade, which positively correlated with the percentage of CD8+ cells (K = 0.4, P = 0.005) and negatively with the percentage of NK cells (K = -0.5, P = 0.005). There was an inverse correlation with the percentage of gamma/delta T cells in PBL and the TIL concentration (K = -0.3, P < 0.05). CONCLUSIONS: The TIL immunophenotype is different from PBL and is influenced by the histological grade of the tumour. The activation of TIL and its relationship with tumour progression suggests that they might be sensitized and activated by tumour cells.

Aged↗

PubMed2000

Expression of CD94/NKG2 subtypes on tumor-infiltrating lymphocytes in primary and metastatic melanoma.

Natural killer receptors are expressed both on natural killer populations and subpopulations of T cells, mainly alpha/beta TCR+CD8+ T cells. We have characterized the expression of the C-type lectin natural killer receptor CD94/NKG2 on tumor-infiltrating lymphocytes in primary and metastatic melanoma lesions. By immunohistochemistry, 5-10% of the tumor-infiltrating lymphocytes, both in primary and metastatic lesions, expressed CD94. More than 95% of these CD94+ cells coexpressed CD8 and the percentage of CD94 expression within the CD8+ cell population ranged from 5 to 20% with a higher expression in metastatic lesions. CD94/NKG2 exists both in an inhibitory and an activating form; thus, it was necessary to determine whether the inhibitory CD94/NKG2-A/B, the activating CD94/NKG2-C/E, or both were expressed on tumor-infiltrating lymphocytes. Reverse transcription-polymerase chain reaction using specific primers for NKG2-A/B and C/E mRNA revealed the presence of NKG2-C/E in all primary and metastatic lesions. In contrast, the inhibitory NKG2-A/B was only present in 50% of primary tumors whereas 80% of tumor-infiltrating lymphocytes in metastatic lesions expressed these transcripts. In healthy humans, the mean number of inhibitory natural killer receptors is higher than that of activating receptors, but the opposite was true for tumor-infiltrating lymphocytes in melanoma. The reversal of the ratio of inhibitory to activating natural killer receptors among tumor-infiltrating lymphocytes suggests a regulated event due to either specific factors within the tumor microenvironment, preferential homing of T cell subsets, or certain stages of T cell activation.

Adult↗

PubMed2001

The tumor-infiltrating B cell response in medullary breast cancer is oligoclonal and directed against the autoantigen actin exposed on the surface of apoptotic cancer cells.

Medullary carcinoma of the breast (MCB) is a morphologically and biologically distinct subtype of human breast cancer that, despite cytologically anaplastic features, has a more favorable prognosis than other types of breast cancer at similar stages of differentiation. It has been proposed that the improved clinical outcome is due, at least in part, to the presence of a prominent lymphoplasmacytic cell infiltrate in the tumor stroma. We studied the B lymphoplasmacytic cell infiltrates in MCB to determine the role of the antibody response produced by the local infiltrating cells. Oligoclonal predominance among tumor-infiltrating B cells in a panel of MCB patients was observed, suggesting that certain B cell clones were expanded, possibly in response to specific tumor-associated stimuli. IgG antibody phage-display libraries were generated from MCB-infiltrating lymphoplasmacytic cells of two patients, and MCB-reactive monoclonal antibodies were retrieved by selection on fresh-frozen MCB tissue sections. Analysis by mass spectrometry revealed that the antigen targeted by the dominant clones in the oligoclonal B lymphoplasmacytic response in both patients was not a cancer-specific antigen but the cytoskeletal protein beta-actin. MCB exhibits an increased rate of apoptosis, and apoptotic MCB cells were shown to expose actin on the cell surface, permitting its recognition by the humoral immune system. Further, actin fragments, similar to those observed after cleavage with the apoptotic protease granzyme B, were observed in MCB tissue. Our results indicate that the major antibody response produced by tumor-infiltrating B lymphoplasmacytic cells are autoimmune in nature and a consequence of the perturbed state of increased MCB apoptosis caused by granzyme B-induced T cell cytotoxicity and/or intrinsic cellular factors of MCB cells.

Actins↗

PubMed2000

Quantitative trait loci modulate neutrophil infiltration in the liver during LPS-induced inflammation.

A crucial aspect of the inflammatory response is the recruitment of activated neutrophils (PMN) to the site of damage. Lytic enzymes and oxygen radicals released by PMN are important in clearing an infection or cellular debris, but can also produce host tissue damage. Failure to properly regulate the inflammatory response contributes to a variety of human diseases like sepsis and multiple organ dysfunction syndrome, the leading cause of morbidity and mortality in surgical intensive care units. Many aspects of human disease pathology, including hepatic PMN infiltration, can be recapitulated in mice using an endotoxic shock model. Six quantitative trait loci that predispose to high infiltration of PMN in hepatic sinusoids after high-dose endotoxin administration were provisionally identified. Two of these loci, Hpi1 and Hpi2 on mouse chromosomes 5 and 13, were mapped to the significant and highly significant level using a low-resolution genome scan on 122 intercross animals. These loci interact epistatically to produce a high degree of PMN infiltration. Intercross and recombinant inbred strain mice with a specific genotype at these loci always had a high infiltration response, indicating that genotype analysis at just these two loci can accurately predict a high PMN infiltration response. Genetic predisposition to the degree of PMN infiltration in the inflammatory response in mice suggests that analogous genetic mechanisms occur in human beings that could be used for diagnostic purposes.

Animals↗

PubMed1995

Helper T cells infiltrating human renal cell carcinomas have the phenotype of activated memory-like T lymphocytes.

Human renal cell carcinomas are characterized by an inflammatory infiltrate containing many T lymphocytes. Attempts to grow T cells from such tumors by culture in interleukin (IL)-2 have yielded heterogeneous populations of cells with functional characteristics typical of lymphokine-activated killer cells obtained by similar culture of cells from peripheral blood mononuclear cells. We examined a panel of surface markers expressed on T lymphocytes to determine if the CD4+ T cells infiltrating human renal cell carcinomas are different from those in peripheral blood mononuclear cells. By flow cytometry analysis the CD4+ T cells in a panel of freshly digested human renal cell carcinoma primary and metastatic tumors expressed the activation markers CD69 and HLA-DR and manifested an increase in CD45RO and a reciprocal decrease in CD45RA expression as compared with peripheral blood CD4+ T cells. This suggests that CD4+ T cells infiltrating renal cell carcinomas are activated and have encountered antigen. However, the expression of the IL-2R alpha chain (CD25) was not different in tumor-infiltrating CD4+ T cells and peripheral blood CD4+ T cells, suggesting that T cells infiltrating human renal cell carcinomas may have a block in proliferative capacity. The general failure of cultured tumor-infiltrating lymphocyte (TIL) from renal cell carcinoma to demonstrate tumor-specific reactivity may be due to the failure of such cells to grow in IL-2.

CD4-Positive T-Lymphocytes↗

PubMed1995

Immunohistochemical features of HLA-DR antigen expression and lymphoid infiltrates in gastric carcinoma after low-dose interleukin-2 and mitomycin C.

We immunohistochemically evaluated lymphoid cell infiltration and HLA-DR antigen expression in gastric tumor tissue obtained from advanced gastric cancer patients 1 day after the completion of the treatment with mitomycin C (MMC) 12 mg/m2 i.v. on day 1 and recombinant interleukin-2 (IL-2) i.v. every 12 h from day 4 through day 8. Then the results were compared with those in 11 patients pretreated with MMC alone, 5 treated with IL-2 alone, and 24 untreated patients. Widespread lymphoid infiltration was observed in 17% of untreated tumors, 27% of MMC-pretreated tumors, and 40% of tumors treated with IL-2 alone. However, 71% of carcinomas pretreated with MMC plus IL-2 exhibited widespread infiltration. The frequency of cases with high-grade infiltration of CD4+ cells was significantly higher in either group of patients treated with MMC alone or MMC plus IL-2. Because the CD8+ cell infiltration was not significantly altered, the ratio of CD4+ to CD8+ cells estimated as being > 1 was more frequently noted in patients given MMC alone or MMC plus IL-2, as compared with untreated control. Furthermore, 86% of tumors pretreated with MMC plus IL-2 exhibited positive HLA-DR antigen expression, whereas 29% of untreated carcinomas did so. MMC or IL-2 alone did not significantly increase HLA-DR expression. These results indicate that the combination of low-dose of IL-2 with MMC enhances the intensity of lymphoid cell infiltration in tumors, with the predominance of CD4+ cells, and HLA-DR antigen expression on tumor cells in patients with advanced gastric carcinoma.

Aged↗

PubMed1992

Immunohistochemical characterization of cellular infiltrates in epidermal tumors induced by two-stage and complete chemical carcinogenesis in mouse skin.

We investigated the population and pattern of the infiltrated cells in both benign and malignant epidermal tumors which were induced chemically with benzo(a)pyrene (B(a)P) in murine skin. In benign papillomas, which were evolved by a two stage carcinogenesis regimen, a slight to mild inflammatory infiltration around the tumors was observed, and cells infiltrating into the tumor nests were rarely seen. In carcinomas, which were produced by a complete carcinogenesis regimen, a dense inflammatory infiltration was observed around the tumor nests. The infiltrated cells were characterized as T-lymphocytes, macrophages, and neutrophils. Natural killer (NK) cells were found around and in the tumor nests, but their number was small. Both T-lymphocytes and macrophages were found to invade the tumor nests in squamous cell carcinoma whose duration was more than four weeks. This experimental carcinogenesis animal model allows the detailed quantitative and functional analysis of the infiltration of immunocompetent cells into epidermal tumors.

Animals↗

PubMed2006

Potential role of natural killer cells in controlling growth and infiltration of AIDS-associated primary effusion lymphoma cells.

Natural killer (NK) cells are an important component of the innate immune response against microbial infections and tumors. Direct involvement of NK cells in tumor growth and infiltration has not yet been demonstrated clearly. Primary effusion lymphoma (PEL) cells were able to produce tumors and ascites very efficiently with infiltration of cells in various organs of T-, B- and NK-cell knock-out NOD/SCID/gammac(null) (NOG) mice within 3 weeks. In contrast, PEL cells formed small tumors at inoculated sites in T- and B-cell knock-out NOD/SCID mice with NK-cells while completely failing to infiltrate into various organs. Immunosupression of NOD/SCID by treatment with an antimurine TM-beta1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhanced tumorigenicity and organ infiltration in comparison with non-treated NOD/SCID mice. Activated human NK cells inhibited tumor growth and infiltration in NOG mice. Our results suggest that NK cells play an important role in growth and infiltration of PEL cells, and activated NK cells could be a promising immunotherapeutic tool against tumor or virus-infected cells either alone or in combination with conventional therapy. The rapid and efficient engraftment of PEL cells in NOG mice also suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of pathogenesis and malignant cell growth.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Uterine leiomyoma with massive lymphoid infiltration: case report and review of the literature.

Uterine leiomyoma with massive lymphoid infiltration is a rare and unusual pathological finding. Only 13 cases have been reported in English literature. A case of uterine leiomyoma showing massive lymphoid infiltration in a 45-year-old woman is described. The tumor was relatively soft compared with usual leiomyomas. Microscopically, the tumor showed the typical features of leiomyoma with moderate to severe lymphocytic infiltrate consisting of mature lymphocytes, a few plasma cells and occasional histiocytes. This cellular infiltration was confined to the leiomyoma. Immunohistochemically, the diffusely infiltrated lymphoid cells were stained by antibodies to CD45RO, CD3 and CD8. Germinal centers were stained by antibodies to CD20 and CD79a. Some CD68+ histiocytes were seen. Lymphoid infiltration within the leiomyoma is a peculiar histological morphology, although the cause is not clear. The recognition of its distinct histological features is important to avoid possible confusion with differential diagnoses including malignant lymphoma, inflammatory pseudotumor and pyomyoma.

Antigens, CD↗

PubMed2005

Intratumoral T-cell infiltrates and MHC class I expression in patients with stage IV melanoma.

The infiltration of tumors by T cells has been shown to correlate with prolonged patients' survival. However, it remains unclear why only some tumors are infiltrated with T cells. This study was designed to investigate possible correlations between intratumoral T-cell infiltrates and the expression of cancer-associated antigens and MHC class I and II molecules in patients with melanoma. Fresh frozen samples from 124 stage IV melanoma patients were analyzed by immunohistochemistry for the expression of Melan-A/MART-1, tyrosinase, gp100, NY-ESO-1, and MHC class I and II. Intratumoral T-cell and B-cell infiltrates were detected by staining with anti-CD4, anti-CD8, anti-CD3, and L26 antibodies. The NY-ESO-1 serum antibody status was assessed by Western blot analysis. Intratumoral CD8+ and CD4+ T cells were detected in 63.9% and 71.3% of patients, respectively. We observed a significant heterogeneity of the expression of the melanocyte differentiation antigens, NY-ESO-1, and MHC class I and II molecules. The only significant correlation was found between the expression of MHC class I and the presence of CD4+ and CD8+ T cells (P < 0.0001). There was a strong association between these two variables with respect to the density and distribution of infiltrating T cells and the pattern of MHC class I expression (focal versus homogenous). Intratumoral T-cell infiltration is closely correlated with the MHC class I expression but not with the expression of differentiation antigens, cancer-associated antigens, or MHC class II molecules. These results may have implications for the definition of prognostic variables and for the identification of patients who may benefit from antigen-specific cancer immunotherapy.

Antibodies, Neoplasm↗

PubMed2006

Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers.

PURPOSE: CD4(+) T cells play a central role in initiating and maintaining anticancer immune responses. However, regulatory CD4(+)CD25(+) T cells which express Foxp3 have also been shown to inhibit antitumor effector T cells. In view of these heterogeneous CD4(+) T-cell populations, this study was designed to determine the prognostic value of various tumor-infiltrating CD4(+) T-cell populations in head and neck squamous cell carcinoma. EXPERIMENTAL DESIGN: Eighty-four newly diagnosed untreated patients with histologically proven primary head and neck squamous cell carcinoma were included in this study. Double or triple immunofluorescence staining was done to assess and quantify the activated CD4(+)CD69(+) T cells, regulatory CD4(+)Foxp3(+) T cells, and mixed CD4(+)CD25(+) T cells comprising both activated and regulatory T cells. RESULTS: On univariate analysis, high levels of tumor-infiltrating CD4(+)CD69(+) T cells were correlated with both better locoregional control (P = 0.01) and longer survival (P = 0.01). Infiltration by regulatory Foxp3(+)CD4(+) T cells was positively associated with a better locoregional control of the tumor. Multivariate analysis showed that the only significant prognostic factors related to locoregional control were T stage (P = 0.02) and CD4(+)Foxp3(+) T-cell infiltration of the tumor (P = 0.02). In the Cox multivariate analysis, only two variables influenced overall survival probability: T stage (P = 0.036) and CD4(+)CD69(+) T-cell infiltration (P = 0.017). CONCLUSION: This study shows that tumor-infiltrating activated CD4(+)CD69(+) T cells are associated with a good prognosis in head and neck squamous cell carcinoma. In addition, regulatory Foxp3(+)CD4(+) T cells are positively correlated with locoregional control may be through down-regulation of harmful inflammatory reaction, which could favor tumor progression.

Antigens, CD↗