PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Lymphocytes, Tumor-Infiltrating”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1992

Reaction patterns of tumor infiltrating lymphocytes in different renal cell carcinomas and oncocytomas.

1. Only clear cell and chromophilic carcinomas of the kidney exhibit a considerable lymphocytic infiltration which is compatible with some immunological responsiveness. Chromophobic carcinomas and benign oncocytomas seem to be immunologically reactive. This reflects the different antigen spectrum and histogenesis of these tumors (Störkel and Jacobi, 1989). Clear cell and chromophilic carcinomas are derived from the proximal tubule and chromophobic carcinomas and oncocytomas from the collecting duct. 2. The tumor periphery seems to be the place of greatest immunological importance, as basic requirements of a sufficient lymphocyte/tumor cell interaction can only be expected there. If these data are taken into account for a therapeutical approach with biological immune modifiers the size of the tumor (tumor burden) and proliferation index must be considered too. This might be a likely explanation for the positive effect of inhaled interleukin-2 on lung metastasis in renal cell cancers. Harvesting of tumor infiltrating lymphocytes for therapeutical purposes should take these findings into account. 3. In spite of dense lymphocytic infiltration only 3% of the tumor infiltrating lymphocytes exhibit the activation marker CD 25. There seems to be a sufficient T cell locomotion in renal cell carcinomas but an insufficient T-cell activation. Whether this fact is induced by lacking cytokine stimulation of involved lymphocytes or by still unknown mediators of the tumor cells is not yet known and needs further investigation. 4. Clear cell carcinomas exhibit most adhesion molecules and the highest amount of infiltrating cytotoxic T-cells and natural killer cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1992

HLA class II antigen expression in human papillomavirus-associated cervical cancer.

The observation that tumor cells of some neoplasms display major histocompatibility complex (MHC) class II molecules may be of functional significance, influencing the progression of malignancy by allowing the cancer cells to present antigen to the immune system. In the normal cervix, class II molecules are expressed by columnar but not squamous epithelium. The pattern of MHC class II expression in cervical carcinomas has been documented using immunohistochemical methods. Of 53 cervical squamous carcinomas examined for MHC class II expression, only 17% maintained a negative phenotype characteristic of the epithelium from which they were derived, while the remaining tumors exhibited either uniform (45%) or heterogeneous (38%) expression. Tumor areas which were class II positive also express class II associated invariant chain and the adhesion molecules lymphocyte function antigen 3 and intercellular adhesion molecule 1. The DR, DP, and DQ class II MHC subloci are differentially expressed, suggesting independent regulation. There is a trend for tumors with the uniform class II phenotype to predominantly express DR antigen, whereas tumors of the heterogeneous class II phenotype express with equal frequency either DR or DP antigens dominantly. There is no apparent influence of class II status on lymphocyte infiltration of the tumors. The presence of human papillomavirus 16 DNA in the cervical carcinoma specimens was analyzed by Southern blotting of restriction enzyme digested DNA and no correlation between the presence of human papilloma virus and MHC class II expression was found.

Adult↗
PubMed1992

Postvaccinal sarcomas in the cat: epidemiology and electron probe microanalytical identification of aluminum.

An increase in fibrosarcomas in a biopsy population of cats in the Pennsylvania area appears to be related to the increased vaccination of cats following enactment of a mandatory rabies vaccination law. The majority of fibrosarcomas arose in sites routinely used by veterinarians for vaccination, and 42 of 198 tumors were surrounded by lymphocytes and macrophages containing foreign material identical to that previously described in postvaccinal inflammatory injection site reactions. Some of the vaccines used have aluminum-based adjuvants, and macrophages surrounding three tumors contained aluminum oxide identified by electron probe microanalysis and imaged by energy-filtered electron microscopy. Persistence of inflammatory and immunological reactions associated with aluminum may predispose the cat to a derangement of its fibrous connective tissue repair response, leading to neoplasia.

Aluminum↗
PubMed1992

Interactions between interleukin-2-activated lymphocytes and vascular endothelium: binding to and migration across specialized and non-specialized endothelia.

A prerequisite for the successful immunotherapy of solid tumours with interleukin-2 (IL-2)-activated lymphocytes is their ability to home to the tumour tissue. Lymphocyte homing is a complex process which is known to involve at least two independently regulated events: adhesion to the luminal surface of vascular endothelium and the subsequent transendothelial migration of lymphocytes. In this study we have used an in vitro model of lymphocyte homing which employs specialized high endothelium to ask whether IL-2-activated lymphocytes are able to migrate across vascular endothelium in order to leave the blood vessel. Both the adhesion of IL-2-activated cells and their migration across monolayers of cultured high endothelial cells (HEC) were increased in comparison with non-activated lymphocytes. The adhesion of IL-2-activated lymphocytes was mediated by lymphocyte function-associated antigen-1 (LFA-1) and a very late activation antigen-4 (VLA-4)-related pathway. LFA-1-dependent adhesion was mediated by ligands on HEC other than the intercellular adhesion molecule-1 (ICAM-1) and the VLA-4-related pathway was mediated by ligands other than the CS1 domain of fibronectin. HEC-adherent lymphocytes were enriched in natural killer (NK) cells and CD8+ T cells which are known to be the tumour-cytotoxic cells in IL-2-activated lymphocytes. However, there was no evidence of cytotoxicity towards the endothelial layer using a syngeneic model. The interaction of IL-2-activated lymphocytes and endothelial cells was not specific for high endothelium since equal numbers of activated lymphocytes bound to and migrated across aortic endothelium. The inability of IL-2-activated lymphocytes to discriminate between high endothelium and non-specialized 'flat' endothelium could be responsible for the widespread dissemination of the cells throughout the body following their adoptive transfer and the unwanted side-effects at non-involved sites.

Animals↗
PubMed1992

Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation.

Interaction of T and B lymphocytes, platelets, granulocytes, macrophages and mast cells with the subendothelial extracellular matrix (ECM) is associated with degradation of heparan sulfate (HS) by a specific endoglycosidase (heparanase) activity. The enzyme is released from intracellular compartments (i.e., lysosomes, specific granules) in response to various activation signals (i.e., thrombin, calcium ionophore, immune complexes, antigens, mitogens), suggesting its regulated involvement in inflammation and cellular immunity. In contrast, various tumor cells appear to express and secrete heparanase in a constitutive manner, in correlation with their metastatic potential. Heparanase enzymes produced by different cell types may exhibit different molecular properties and substrate cleavage specificities. The platelet enzyme appears also in a latent form. It can be activated by tumor cells and thereby facilitate their extravasation in the process of metastasis. Degradation of ECM-HS by all cell types was facilitated by a proteolytic activity residing in the ECM and/or expressed by the invading cells. This proteolytic activity produced a more accessible substrate for the heparanase enzymes. Heparanase-inhibiting, nonanticoagulant species of heparin markedly reduced the incidence of lung metastasis in experimental animals. These species of heparin also significantly impaired the traffic of T lymphocytes and suppressed cellular immune reactivity and experimental autoimmune diseases. Heparanase activity expressed by intact cells (i.e., platelets, mast cells, neutrophils, lymphoma cells) was found to release active HS-bound basic fibroblast growth factor from ECM and basement membranes. Heparanase may thus elicit an indirect neovascular response in processes such as wound repair, inflammation and tumor development. The significant anticancerous effect of heparanase-inhibiting molecules may therefore be attributed to their potential inhibition of both tumor invasion and angiogenesis. Both normal leukocytic cells and metastatic tumor cells can enter the bloodstream, travel to distant sites and extravasate to the parenchyma at these sites. We suggest that heparanase is utilized for this purpose by both types of cells. Other functions (i.e., enzyme activities, adhesive interactions, chemotactic and proliferative responses) of metastatic tumor cells seem to mimic the equivalent functions of leukocytes as they migrate across blood vessels to gain access to sites of inflammation.

Animals↗
PubMed1992

[Lymphoid infiltration of colon cancer and clinical significance of the skin test].

It was reported that lymphoid infiltration (LI) of colon cancer tended to be found more commonly in patients with colonic cancer in an early stage than in an advanced stage. This time, the correlation among LI of colon cancer, cell-mediated immunity and the cumulative 5-year survival rate was studied in 124 patients with resected colon cancer. The results were as follows: 1) The cumulative 5-year survival rate in patients with positive LI was higher than that in the patients with negative LI. 2) There was correlation between the degree of LI of the cancer and Su-PS skin reaction. 3) Postoperative cell-mediated immunity was reduced in the cases of poor prognosis. Therefore we insist on paying attention to immunochemotherapy for 24 months after surgery.

Colonic Neoplasms↗
PubMed1992

[Primary malignant lymphoma of the parotid gland. Report of a case].

Primary malignant lymphoma of the parotid gland is often correlated, in literature data, with inflammatory autoimmunological disease of the salivary gland. Finding of blasticlymphoid cells in myoepithelial scialoadenitic areas in a case of parotid disease is described by the Authors. Needle may be useful in detecting these high radio-chemosensitive neoplasms to reduce the occurrence of complications of total parotidectomy.

Aged↗
PubMed1992

[The motility of IL-2 activated lymphocytes into malignant glioma].

The effects of glioma culture supernatant (GCS) and interleukin-2(IL-2) on the motility of autologous stimulated lymphocytes (ASL) were studied by using collagen gel system, chemotaxic chamber system and flow cytometric analysis. GCS inhibited the migration of ASL into collagen gel. It enhanced the ASL motility and the expression of CD 26 antigen on the cell surface. IL-2 inhibited the migration of ASL into collagen gel and had no influence on the motility of ASL, but enhanced the expression of CD 26 antigen. On the other hand, a clinical glioma specimen showed limited depth of ASL migration when injected into the tumor cavity in addition to the formation of fibrin like membrane on its surface and a layer of degenerated ASL under it. To make ASL therapy more effective to malignant glioma, the following measures should be recommended; 1) inject adequate volume of IL-2 into tumor cavity, 2) reduce the frequency of ASL administration, 3) wash out of glioma secreting factors, degenerated ASL and glioma cells in addition to reduce the volume of tumor tissue.

Cell Movement↗
PubMedDate not supplied

The influence of tumor lymphocytic infiltration on long term survival of surgically treated colorectal cancer patients.

Prognostic significance of host-immune response, as gathered by the degree of tumour lymphocytic infiltration (TLI), and its relationship to other prognostic variables were investigated in 361 colorectal cancer patients admitted to our Institution for curative resection from January 1960 to December 1978. The presence of a local immune reactivity was significantly related to a less advanced stage of disease and a better differentiated tumour. A poorer prognosis was detected in patients with minor or no lymphocytic infiltration. TLI was the single most important prognostic parameter, according to the Cox model and to logistic regression analysis. These findings suggest that also TLI should be considered in the current Staging System of colorectal cancer.

Adult↗
PubMedDate not supplied

Non-Hodgkin's lymphoma and Sjögren's syndrome. An immunopathological study of 113 patients.

One hundred and thirteen patients with untreated non-Hodgkin's lymphoma were evaluated for Sjögren's syndrome (SS) using clinical and biological parameters, and a minor salivary gland biopsy. Concomitant immunophenotyping for T and B cells, and kappa and lambda chains was performed on both minor salivary gland and lymphomatous tissues. Patients with a positive focus score on examination of their minor salivary gland biopsy had a second biopsy, when possible, at the end of induction therapy. Fourteen of the 113 patients had SS according to the Greek criteria, and 4 of these 14 patients had an identical monotypic infiltrate in both their minor salivary gland and lymphomatous tissues. In all four cases this infiltrate disappeared from both locations when the lymphoma was in complete remission (CR). The 10 other patients with criteria for SS had a mixed infiltrate which persisted unchanged when the lymphoma was in CR. Among the 99 patients without SS, 12 had a positive focus score and an identical monotypic infiltrate in both their minor salivary gland and lymphomatous tissue. This infiltrate disappeared from both locations when the lymphoma was in CR. Among the remaining 87 patients, 82 had no minor salivary gland infiltrate, and 5 had a positive focus score with mixed lymphocytic infiltrate. Long term follow up and a large cooperative study are needed to better understand the immunopathologic lesions of patients of this latter type.

Adult↗
PubMed1992

Engraftment of human peripheral blood leukocytes into severe combined immunodeficient mice results in the long term and dynamic production of human xenoreactive antibodies.

Severe combined immunodeficient (SCID) mice engrafted with human peripheral blood leukocytes (hu-PBL-SCID) represent a potentially important small animal model for the study of human immune function. Attempts to generate human primary immune responses to exogenous Ag in the hu-PBL-SCID have had limited success which raises questions about the functional capacity of human lymphocytes in the SCID environment. Here, we demonstrate that the spontaneously secreted human Ig in hu-PBL-SCID includes antibodies with specificity for several different mouse RBC (mRBC) proteins. These antibodies apparently reflect the transfer of peripheral B cells which are responsible for the production of naturally occurring xenoreactive antibodies in the donor. Western blot analysis showed that engraftment of anti-mRBC specificities was random among mice receiving PBL from the same donor sample. In at least one mouse, this engraftment was polyclonal and included human IgM and IgG which recognized at least 12 different mRBC proteins ranging in size from 35 to > 200 kDa. Anti-mRBC specificities were found to vary with time demonstrating a dynamic expression of the human xenoreactive repertoire in hu-PBL-SCID. In contrast to mice engrafted with human PBL, mice engrafted with another source of human B cells, i.e., tumor-infiltrating leukocytes, produced very little or no human anti-mRBC antibody. Ag-driven proliferation of xenoreactive clones may result in a skewing of the engrafted human B cells in hu-PBL-SCID which could account in part for the limited ability of hu-PBL-SCID to respond to exogenous Ag. The long term production of anti-mRBC antibodies and the modulation of the expressed xenoreactive repertoire observed in hu-PBL-SCID represents an opportunity to study the molecular genetics and cell biology of the human humoral immune response to a defined complex Ag.

Adsorption↗
PubMed2026

MIF-CD74 axis facilitates MDSC infiltration in the tumor microenvironment of pancreatic ductal adenocarcinoma.

Immune checkpoint inhibitors show insufficient efficacy against pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment (TME) has a remarkable influence on responsiveness to cancer immunotherapy. The aim of this study was to investigate immunosuppressive characteristics of TME in PDAC tissues. The flow cytometry (FCM) of PDAC surgical specimens revealed that the profile of tumor-infiltrating leukocytes was classified into myeloid cell- and T-cell-dominant subtypes; the myeloid subtype was associated with poorer patient outcomes. Myeloid-derived suppressor cells (MDSCs) showed the highest hazard ratio among various myeloid cell types. Single-cell RNA sequencing and FCM revealed that most MDSCs, but not lymphocytes, in PDAC tissues characteristically express CD74. Macrophage migration inhibitory factor (MIF), a CD74 ligand, was highly expressed in cancer-associated fibroblasts (CAFs) and cancer cells. Spatial transcriptomics demonstrated that the MIF-CD74+ myeloid cell interaction was recognized in CAF-dominant areas in PDAC tissue. CAFs expressing immune suppressor molecules such as MFAP5 and LRRC15 were consistent with MIF+ CAFs. Furthermore, MIF+ CAFs enhanced the migratory activity of MDSCs and promoted MDSC induction and activation. In the murine model, MDSCs were significantly increased in MIF-expressing PDAC tumors, as were CD74+ M-MDSCs per M-MDSC, confirming in vivo interaction between CD74 and MIF. MDSCs play a crucial role in creating an immunosuppressive TME in PDAC; the MIF-CD74 axis drives interactions between MDSCs and CAFs.

Humans↗
PubMed2026

In vivo genome-wide CRISPR screens identify FOXR1 as a suppressor of CD8+ T cell antitumor immunity.

T cell dysfunction critically limits the efficacy of T cell-based immunotherapies in solid tumors, yet the intrinsic regulators of T cell dysfunction remain incompletely understood. Through an in vivo genome-wide CRISPR screen in tumor-infiltrating CD8+ T cells, we identified Forkhead Box R1 (FOXR1) as a potent transcriptional suppressor of CD8+ T cell effector functions. Genetic ablation of FOXR1 significantly enhanced cytokine production and cytotoxic capacity in both murine and human CD8+ T cells, whereas its overexpression impaired T cell activation and effector molecule expression. Mechanistically, multiomics integration of RNA-seq, CUT&Tag-seq, and ATAC-seq revealed that FOXR1 binds directly to promoter regions of key effector genes, including IL2, GZMB, and PRF1, and represses their expression. Importantly, FOXR1 deletion in human anti-CD19 CAR T cells improved their efficacy against solid tumors, demonstrating that FOXR1 is a checkpoint of T cell effector function and targeting FOXR1 is a promising strategy to enhance CAR T cell efficacy against solid tumors.

Animals↗
PubMed2026

A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.

PURPOSE: Survival for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) remains low with <20% immunotherapy response. Metformin increases tumor-infiltrating CD8+ T and natural killer (NK) cells, which harbor PD-1. In this phase II clinical trial (NCT04414540), we combined metformin and pembrolizumab to evaluate the overall response rate (ORR) in R/M HNSCC and assess NK-cell activity. PATIENTS AND METHODS: Eligible patients were randomized 1:1 into two arms: (i) metformin extended-release (ER) dose escalation to 2,000 mg over 14 days followed by combination with pembrolizumab 200 mg every 3 weeks or (ii) pembrolizumab 200 mg every 3 weeks followed by combination with metformin ER 2,000 mg daily. The primary endpoint was ORR per RECIST 1.1. Nineteen evaluable patients were planned to estimate the proportion of approximately 32% ORR. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0. The distribution, activation, and cytotoxic function of NK cells were analyzed via flow cytometry. RESULTS: Twenty-one patients were enrolled; 76% were male, 52% were smokers, and the median age was 64 years. Ten patients had oropharyngeal tumors, of which nine were p16+. Eighteen patients were evaluable for response, including four complete and five partial responses for an ORR of 50% [95% confidence interval (29-71)]. Combination therapy was well tolerated with no unexpected adverse events (AE). Five grade 3 AEs occurred: nausea, diarrhea, fatigue, and weight loss. Metformin led to increased peripheral NK-cell maturation and cytotoxic ability. CONCLUSIONS: The combination of metformin and pembrolizumab was well tolerated with mild gastrointestinal AEs and promising activity, warranting further investigation in a randomized trial.

Humans↗