Lymphoid Aggregates Research Articles

Cutaneous T cell lymphoma atlas reveals malignant TH2 cells supported by a B cell-rich tumor microenvironment

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (TH2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II+ fibroblasts and dendritic cells that can maintain TH2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL.

Cancer-Associated Lymphoid Aggregates in Histology Images: Manual and Deep Learning-Based Quantification Approaches.

Quantification of lymphoid aggregates including tertiary lymphoid structures (TLS) with germinal centers in histology images of cancer is a promising approach for developing prognostic and predictive tissue biomarkers. In this article, we provide recommendations for identifying lymphoid aggregates in tissue sections from routine pathology workflows such as hematoxylin and eosin staining. To overcome the intrinsic variability associated with manual image analysis (such as subjective decision-making, attention span), we recently developed a deep learning-based algorithm called HookNet-TLS to detect lymphoid aggregates and germinal centers in various tissues. Here, we additionally provide a guideline for using manually annotated images for training and implementing HookNet-TLS for automated and objective quantification of lymphoid aggregates in various cancer types.

Laser Capture Microdissection of Tertiary Lymphoid Structures from Formalin-Fixed Paraffin-Embedded Sections of Canine Cutaneous and Subcutaneous Sarcomas for NanoString Direct RNA Counting.

Laser capture microdissection (LCM) of formalin-fixed, paraffin-embedded sections is a way to analyze gene expression of morphologically distinct areas of tissue, as microscopically visualized with stained tissue sections. Herein, I describe a method for laser dissecting lymphoid aggregates in canine cutaneous and subcutaneous sarcomas and their adjacent sarcoma tissue to determine the differential expression of RNA as determined by NanoString® nCounter technology. Canine soft tissue sarcomas (STS) are diversely derived mesenchymal neoplasms that, regardless of exact histogenesis, behave similarly and thus have been grouped together as a diagnostic entity. The risk of recurrence and/or metastasis depends on the extent of surgical excision and histologic grade. Lymphoid aggregates are described in these tumors but have not been characterized. In humans, lymphoid aggregates characterized as tertiary lymphoid structures (TLS) improve the prognosis of several tumors, including sarcomas. We sought to determine if RNA expressed by lymphoid aggregates in canine sarcomas was compatible with TLS RNA expression. This chapter describes tissue preparation, staining, laser capture microdissection, and RNA isolation in preparation for digital RNA counting.

Mouse Models Enable the Functional Investigation of Tertiary Lymphoid Structures in Cancer.

Tertiary lymphoid structures (TLSs) are organized lymphoid aggregates that form within nonlymphoid tissue, including tumors, in response to persistent inflammatory stimulation. In cancer patients, TLSs are generally associated with positive clinical outcomes. However, the cellular composition and spatial distribution of TLSs can vary depending on the underlying disease state, complicating interpretations of their prognostic significance. Murine models are indispensable for providing a deeper insight into the mechanisms involved in TLS formation and function. Studies using these models can complement current clinical efforts to characterize TLSs via genetic sequencing and histopathology of human samples. Several features of TLSs resemble that of secondary lymphoid organs (SLOs). Consequently, vascular system components and structural support elements are important for TLS formation and maintenance. Furthermore, TLSs in different tissue environments can exhibit distinct characteristics, necessitating careful consideration when selecting mouse models for study. Herein, we discuss critical aspects to consider when modeling TLSs and describe recent findings of TLS studies in the mouse lung and intestinal gut environments as examples to highlight the importance of considering tissue-specific regulatory mechanisms for TLSs. In this chapter, we also summarize the mechanistic insights derived from murine models on the formation and function of TLSs, which may translate to the future therapeutic modulation of TLS in disease.

TMIC-39. SPATIAL MULTIOMICS PROFILING REVEALS HETEROGENEITY OF B:T CELL INTERACTIONS AND PLASMA CELL FORMATION IN TERTIARY LYMPHOID STRUCTURES IN HUMAN GLIOMAS

Abstract Adult-type diffuse gliomas, the most common primary brain tumours, remain a clinical challenge in oncology with limited treatment options, restricted anti-tumour immune response and a dismal patient prognosis. Despite their immunosuppressive microenvironment, the formation of lymphoid aggregates containing adaptive immune cells has been reported in gliomas. However, the cellular compositions, immunological function, and relevance of lymphoid aggregates for adaptive anti-tumour immunity is not well understood. Therefore, we performed a comprehensive, unbiased analysis of lymphoid aggregation in 642 adult-type diffuse gliomas using a multi-modal approach, combining DNA methylation and RNA sequencing with spatial transcriptome and proteome profiling. Overall, B cell aggregates and tertiary lymphoid structures (TLS) were observed in 15% of tumours, with the highest prevalence in primary glioma localised to the temporoparietal lobe. The presence of TLS was associated with an improved overall survival. Gliomas containing TLS displayed a remodelled perivascular space, characterised by transcriptional upregulation and spatial redistribution of collagens associated with barrier functions. Spatial transcriptome and proteome profiling revealed heterogenous B:T cell interactions that were associated with elevated CD8 T-cell numbers and differences in IgA and IgG plasma cell forming capacity, suggestive of dynamic adaptive immune response.

Machine Vision–Detected Peritumoral Lymphocytic Aggregates Are Associated With Disease-Free Survival in Patients With Papillary Thyroid Carcinoma

Papillary thyroid carcinoma (PTC) is the most prevalent form of thyroid cancer, with a disease recurrence rate of around 20%. Lymphoid formations, which occur in nonlymphoid tissues during chronic inflammatory, infectious, and immune responses, have been linked with tumor suppression. Lymphoid aggregates potentially enhance the body’s antitumor response, offering an avenue for attracting tumor-infiltrating lymphocytes and fostering their coordination. Increasing evidence highlights the role of lymphoid aggregate density in managing tumor invasion and metastasis, with a favorable impact noted on overall and disease-free survival (DFS) across various cancer types. In this study, we present a machine vision model to predict recurrence in different histologic subtypes of PTC using measurements related to peritumoral lymphoid aggregate density. We demonstrate that quantifying peritumoral lymphocytic presence not only is associated with better prognosis but also, along with tumor-infiltrating lymphocytes within the tumor, adds additional prognostic value in the absence of well-known second mutations including TERT. Annotations of peritumoral lymphoid aggregates on 171 well-differentiated PTCs in the Cancer Genome Atlas Thyroid Carcinoma (TCGA-THCA) data set were used to train a deep-learning model to predict regions of lymphoid aggregates across the entire tissue. The fractional area of the tissue regions covered by these lymphocytes was dichotomized to determine the following 2 risk groups: a significant and low density of peritumoral lymphocytes. DFS prognosticated using these risk groups via the Kaplan-Meier analysis revealed a hazard ratio (HR) of 2.51 (95% CI: 2.36, 2.66), tested on 170 new patients also from the TCGA-THCA data set. The prognostic performance of peritumoral lymphocyte aggregate density was compared against the univariate Kaplan-Meier analysis of DFS using the fractional area of intratumoral lymphocytes within the primary tumor with an HR of 2.04 (95% CI: 1.89, 2.19). Combining the lymphocyte features in and around the tumor yielded a statistically significant improvement in prognostic performance (HR, 3.17 [95% CI: 3.02, 3.32]) on training and were independently evaluated against 62 patients outside TCGA-THCA with an HR of 2.44 (95% CI: 2.19, 2.69). Multivariable Cox regression analysis on the validation set revealed that the density of peritumoral and intratumoral lymphocytes was prognostic independent of histologic subtype with a concordance index of 0.815.

Differences in the pathological, transcriptomic, and prognostic implications of lymphoid structures between primary and metastatic cutaneous melanomas

BackgroundWhile the prognostic role of tertiary lymphoid structures (TLS) has been well studied in solid cancers, the prevalence and impact of immature precursor lymphoid structures known as lymphoid aggregates (LA)...

Neurofibroma-like Desmoplastic Melanoma: A Series of Five Cases Exploring the Role of Molecular Testing as a Diagnostic Adjunct and Highlighting the Differential Diagnosis With Diffuse-type Neurofibroma.

A subset of desmoplastic melanomas (DMs) can show extensive morphologic and immunohistochemical overlap with cutaneous diffuse-type neurofibroma. Neurofibroma-like desmoplastic melanoma (NFLDM) thus poses a significant diagnostic pitfall because the clinical implications of these 2 entities differ dramatically. A series of 17 DMs, including 5 cases of NFLDM, were compared with a cohort of 53 cutaneous diffuse-type neurofibromas to explore the utility of molecular testing in the differential diagnosis between NFLDM and neurofibroma and to determine potentially useful morphologic features in this differential diagnosis. Unlike NFLDM, cutaneous diffuse-type neurofibromas: (1) rarely feature intratumoral or peritumoral lymphoid aggregates, (2) consistently harbor an intrinsic stromal support vasculature composed of evenly spaced capillary-sized vessels, and (3) infiltrate adjacent adipose tissue in a dermatofibrosarcoma protuberans-like manner with a complete lack of chronic inflammation or fat necrosis at the leading edge of the tumor. Conversely, DMs, including NFLDM: (1) do not contain Wagner-Meissner bodies, (2) often induce fat necrosis and/or chronic inflammation at the interface with adjacent fibroadipose tissue, (3) lack the intrinsic capillary-sized stromal vasculature observed in most neurofibromas, and (4) may harbor foci of perineuriomatous differentiation, mimicking a hybrid nerve sheath tumor. Any deviation from the expected clinical or morphologic features of cutaneous diffuse-type neurofibroma should raise suspicion for NFLDM. Although not entirely sensitive or specific, molecular testing can help to support the diagnosis of NFLDM by demonstrating genetic abnormalities associated with melanoma, including a UV-light-induced mutational signature, high tumor mutational burden, and/or chromosomal copy number alterations typical of melanoma.

Lymphoid Aggregates in Canine Cutaneous and Subcutaneous Sarcomas: Immunohistochemical and Gene Expression Evidence for Tertiary Lymphoid Structures.

Canine cutaneous/subcutaneous soft-tissue sarcomas (STS) are diversely derived mesenchymal neoplasms with a risk of recurrence and/or metastasis depending on the extent of surgical excision and histologic grade. Lymphoid aggregates (LAs) are often described in these tumours but not characterised. In humans, LA characterised as tertiary lymphoid structures (TLSs) improve the prognosis of many tumours, including sarcomas. We sought to determine if LA meeting a size criterion (> 700 cells) in canine sarcomas met the criteria of TLS and the overall prevalence of LA of any size. RNA expression in large LAs versus aggregate-adjacent sarcoma tissue (AAS) was measured in laser capture microdissected tissue and compared to curl-derived RNA from aggregate-free sarcomas and lymph nodes. CD3, CD20, MUM-1 and PNAd expressions were measured using immunohistochemistry. CD20 and CD3 mRNA were more highly expressed in LA versus AAS (13.8 fold, p = 0.0003 and 2.3 fold, p = 0.043). This was supported by the IHC findings. The large LAs were also enriched in chemokine RNA expression characteristic of TLS (CXCR5 5.8 fold, p < 00001, CCL19 3.68 fold, p = 0.0209, CCL21 6.87 fold, p = 0.0209 and CXCL13 2.68 fold, p = 0.0924). Plasma cells and high endothelial venules were identified in LA containing tumours but not in control tissue. Large LAs were present in 12% of tumours, and LA of any size in 30%. We conclude that large LAs in canine STS are consistent with TLS.

Histopathological Features of Chronic Gastritis and its Association with Helicobacter pylori Infection.

A Helicobacter pylori (H. pylori) infection is the most common cause of chronic gastritis (CG), with approximately 50% of the world's population infected. Long-term infection increases the risk of progression to gastric cancer. This study evaluated the histopathological changes in CG using the Updated Sydney System (USS) to estimate the prevalence and correlation of H. pylori gastritis with other histological variables. This research was a prospective observational study conducted in the Department of Pathology of a tertiary care teaching hospital in Central India. The study was conducted between Feb 2017 to April 2018. Two antral biopsies were taken per patient, one for a Rapid Urease Test and the second for routine histopathology. All samples were analyzed according to the USS. CG was found in 83.84% of total dyspeptic patients. The most common age group was 31-40 years, with a male preponderance. Of 109 gastric antral biopsies with histopathological evidence of chronic gastritis, neutrophilic activity, intestinal metaplasia, atrophy, and lymphoid aggregates were present in 50 (45.87%), 10 (9.2%), 23 (21.10%), and 11(10.09%) cases, respectively. The prevalence of H. pylori was 46.78%, and its association with the degree of chronic inflammation and intestinal metaplasia was statistically significant. H. pylori was significantly associated with the degree of chronic inflammation and intestinal metaplasia. Hence, this study suggests a vigorous search for H. pylori should be initiated if chronic inflammation and intestinal metaplasia are seen in antral gastric biopsies.

Alum-anchored IL-12 combined with cytotoxic chemotherapy and immune checkpoint blockade enhanced antitumor immune responses in head and neck cancer models

BackgroundFirst-line treatment with pembrolizumab plus chemotherapy in recurrent and metastatic head and neck squamous cell carcinomas (HNSCC) has improved survival. However, the overall response rate with this standard of care...

Maturity and density of tertiary lymphoid structures associate with tumor metastasis and chemotherapy response.

Tertiary Lymphoid Structures (TLSs) are abnormal clusters of immune cells that form in tissues not normally associated with the immune system, usually in cases of long-lasting inflammation, like cancer. TLSs have been suggested as a potential prognostic indicator in various cancer types. We retrospectively enrolled 223 gastric cancer (GC) patients who had surgical resections in this study. We utilized hematoxylin and eosin (HE) staining to detect the presence, abundance, and maturity of TLSs. In serial sections, we used immunohistochemistry to examine the cellular composition of TLSs. The pathological review identified TLSs in 95.1% of the tumors, lymphoid aggregates in 79.8%, primary follicles in 45.7%, and lymphoid aggregates in 95.1% of the cases. Based on Kaplan-Meier curves, the maturation and abundance of TLSs contributed to longer disease-free survival (DFS) and overall survival (OS). In addition, the density of TLSs was strongly associated with the occurrence of tumor metastases and the response to adjuvant chemotherapy. We validated the prognostic value of TLSs in GC patients in both independent cohorts, and the maturity and density of TLS correlated with tumor metastasis. In addition, TLS may reflect sustained antitumor potency, which has important implications for adjuvant chemotherapy.

Prognostic significance of tertiary lymphoid structures in gastric neuroendocrine carcinoma with association to delta-like ligand 3 and neuroendocrine expressions.

Gastric neuroendocrine carcinomas (NECs) are rare cancers with highly aggressive behavior. Although tertiary lymphoid structures (TLSs) are well-known prognostic factors in various cancers, their role in gastric NECs remain unexplored. Unique immunohistochemical subtypes of pulmonary NECs have been discovered, however, their feasibility in gastric NECs is unknown. The presence and maturation of TLSs (lymphoid aggregates, primary and secondary follicles) were assessed in 48 surgically resected gastric NECs and were compared with immunohistochemical subtypes, using a panel of ASCL1, NeuroD1, POU2F3, YAP1, and DLL3 with three neuroendocrine (NE) markers. Patients with secondary follicles had significantly better overall survival (OS) and recurrence-free survival (RFS; both, p = 0.004) than those without them. Based on the hierarchical clustering, gastric NECs were classified into all low/negative (31%), high-YAP1 (19%), high-DLL3/low-NE (29%), and high-NE (21%) expression groups. The high-DLL3/low-NE group was associated with absent TLSs (p = 0.026) and showed the worst OS (p = 0.026). Distant metastasis and a lack of secondary follicles were poor independent prognostic factors of OS and RFS. The assessment of TLSs is a feasible and potent biomarker for gastric NECs, thus enabling better prognosis and moreeffective immunotherapy. Furthermore, gastric NECs can be categorized as four immunohistochemically distinct groups, of which the high-DLL3/low-NE group has the worst OS with lack of TLSs.

Pancreatic cancer cells overexpressing interleukin 6 induce T-cell-mediated tumor clearance and durable anti-tumor immune response.

Tumor immune resistance is recognized as a contributor to low survivorship in pancreatic ductal adenocarcinoma (PDAC). We developed a novel murine model of spontaneous PDAC clearance, generated by overexpressing interleukin-6 (IL-6) in orthotopically implanted PDAC cancer cells (OT-PDACIL6). Circulating IL-6 was 100-fold higher in OT-PDACIL6 than in OT-PDACparental mice. OT-PDACIL6 tumors were present at 5 days post-implantation, and undetectable by 10 days post implantation. Flow cytometry revealed increased T cells and NK cells, and decreased T regulatory cells in OT-PDACIL6 as compared to OT-PDACparental tumors. Increased lymphoid aggregates were apparent by histological assessment and may account for elevated T cell content. Antibody-based depletion of CD4+ and CD8+ T cells prevented tumor clearance and significantly reduced survival of OT-PDACIL6 mice. The anti-tumor immune response to OT-PDACIL6 rendered mice immune to re-challenge with OT-PDACparental tumors. In high concentrations, IL-6 acts in opposition to previously described pro-tumorigenic effects by enhancing the T cell-mediated anti-tumor response to PDAC.

Mapping Human Immunity and the Education of Waldeyer's Ring.

The development and deployment of single-cell genomic technologies have driven a resolution revolution in our understanding of the immune system, providing unprecedented insight into the diversity of immune cells present throughout the body and their function in health and disease. Waldeyer's ring is the collective name for the lymphoid tissue aggregations of the upper aerodigestive tract, comprising the palatine, pharyngeal (adenoids), lingual, and tubal tonsils. These tonsils are the first immune sentinels encountered by ingested and inhaled antigens and are responsible for mounting the first wave of adaptive immune response. An effective mucosal immune response is critical to neutralizing infection in the upper airway and preventing systemic spread, and dysfunctional immune responses can result in ear, nose, and throat pathologies. This review uses Waldeyer's ring to demonstrate how single-cell technologies are being applied to advance our understanding of the immune system and highlight directions for future research.

Tertiary lymphoid structures and their therapeutic implications in cancer.

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates formed by the structured accumulation of immune cells such as B cells and T cells in non-lymphoid tissues induced by infection, inflammation, and tumors. They play a crucial role in the immune response, particularly in association with tumor development, where they primarily exert anti-tumor immune functions during tumorigenesis. Current research suggests that TLSs inhibit tumor growth by facilitating immune cell infiltration and are correlated with favorable prognosis in various solid tumors, serving as an indicator of immunotherapy effectiveness to some extent. Therefore, TLSs hold great promise as a valuable biomarker. Most importantly, immunotherapies aimed to prompting TLSs formation are anticipated to be potent adjuncts to current cancer treatment. This review focuses on the formation process of TLSs and their potential applications in cancer therapy.

Tertiary lymphoid structures in anticancer immunity.

Tertiary lymphoid structures (TLS) are transient ectopic lymphoid aggregates where adaptive antitumour cellular and humoral responses can be elaborated. Initially described in non-small cell lung cancer as functional immune lymphoid structures associated with better clinical outcome, TLS have also been found in many other carcinomas, as well as melanomas and sarcomas, and associated with improved response to immunotherapy. The manipulation of TLS as a therapeutic strategy is now coming of age owing to the likely role of TLS in the improved survival of patients with cancer receiving immune checkpoint inhibitor treatment. TLS have also garnered considerable interest as a predictive biomarker of the response to antitumour therapies, including immune checkpoint blockade and, possibly, chemotherapy. However, several important questions still remain regarding the definition of TLS in terms of both their cellular composition and functions. Here, we summarize the current views on the composition of TLS at different stages of their development. We also discuss the role of B cells and T cells associated with TLS and their dialogue in mounting antibody and cellular antitumour responses, as well as some of the various mechanisms that negatively regulate antitumour activity of TLS. The prognostic value of TLS to the clinical outcome of patients with cancer and the relationship between TLS and the response to therapy are then addressed. Finally, we present some preclinical evidence that favours the idea that manipulating the formation and function of TLS could lead to a potent next-generation cancer immunotherapy.

Local intragraft humoral immune responses in chronic lung allograft dysfunction

IntroductionDonor human leukocyte antigen (HLA)-specific antibodies (DSA) and non-HLA antibodies can cause allograft injury, possibly leading to chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx). It remains unclear whether these antibodies are produced locally in the graft or derived solely from circulating plasma cells. We hypothesized that DSA and non-HLA antibodies are produced in CLAD lungs. MethodsLung tissue was prospectively collected from 15 CLAD patients undergoing re-LTx or autopsy. 0.3g of fresh lung tissue was cultured for 4 days without or with lipopolysaccharide or with CD40L: resulting lung culture supernatant (LCS) was sampled. Protein eluate was obtained from 0.3g of frozen lung tissue. Mean fluorescence intensity (MFI) of DSA and non-HLA antibodies was measured by Luminex and antigen microarray, respectively. ResultsLCS from all 4 patients who had serum DSA at lung isolation were positive for DSA, with higher levels measured after lung tissue stimulation with CD40L (CD40L+LCS). Of these, only 2 had detectable DSA in the lung eluate. MFI of non-HLA antibodies from CD40L+LCS correlated with those from lung eluate, but not with those from sera. Flow cytometry showed higher frequencies of activated lung B cells for patients whose CD40L+LCS was positive for DSA (n=4) or high non-HLA antibodies (n=6) compared to those with low local antibodies (n=5). Immunofluorescence staining showed CLAD lung lymphoid aggregates with local antibodies contained larger numbers of IgG+ plasma cells and greater IL-21 expression. ConclusionsWe show that DSA and non-HLA antibodies can be produced within activated B cell-rich lung allografts.

Spatial tertiary lymphoid structures imply response to anti-PD-1 plus anlotinib in advanced non-small cell lung cancer.

Despite breakthroughs of immunotherapy synergistically combined with blockade of vascular endothelial growth factor receptor, several patients with advanced non-small cell lung cancer (NSCLC) experience non-response or followed relapse. Organized lymphoid aggregates, termed tertiary lymphoid structures (TLSs), are found to be associated with improved response to immunotherapy. Here, we explore the landscapes of TLSs in tumour tissues from a real-world retrospective study. Our investigation showed that with a median follow-up of 11.2 months, the ORR was 28.6% (18/63, 95% CI 17.9-41.3) and the median PFS was 6.1 (95% CI 5.5-6.6) months in NSCLC patients treated with PD-1 blockade combined with anlotinib. By multiplex immunofluorescence (mIF) analysis, spatially, more TLSs and high CD20+ B-cell ratio in TLSs were associated with higher ORR. High density of intratumoral CD8+ T cells showed better ORR and PFS. The numbers of CD8+ T cells with a distance within 20 μm and 20-50 μm between tumour cells were higher in responders than non-responders. But responders had significantly higher TLSs within 20 μm rather than within 20-50 μm of tumour cells than non-responders. The inflamed immunophenotyping occupied higher proportions in responders and was associated with better PFS. Besides, tumour cells in non-responders were found more temporal cell-in-cell structures than responders, which could protect inner cells from T-cell attacks. Taken together, landscape of TLSs and proximity architecture may imply superior responses to PD-1 blockade combined with anlotinib for patients with advanced non-small cell lung cancer.

Investigation of antigen-presenting cells in the intestinal mesentery in normal and adhesive processes

The morphology and topography of dendritic cells in the mesentery of the small intestine, their quantity, and their presence under normal conditions and during progressive adhesive processes have been insufficiently studied, presenting an important issue in immunomorphology. This study aimed to identify and determine the functional activity of antigen-presenting cells using lectin histochemistry with peanut and lentil lectins under normal conditions and during adhesive processes. The methods employed included morphometric analysis, lectin histochemistry, and statistical analysis. For the first time, using lectin histochemistry with lentil and soy lectins, functionally active and immunologically immature antigen-presenting cells were found in the structure of lymphoid clusters of the small intestine mesentery. A correlation was established between the progression of adhesion processes and the number of antigen-presenting cells. Correlation between dendritic cells and the quantity of immunologically immature lymphocytes and B-lymphocytes was identified, enhancing the understanding of the functional mechanisms of the local arm of innate immunity. An increasing trend in immunologically immature lymphocytes and B-lymphocytes was observed alongside an increase in antigen presenting cells. The results indicated that the activation of dendritic cells in mesenteric tissues induced an increase in immunologically immature lymphocytes, from which B-lymphocytes subsequently developed, initiating a local immune response. The increased frequency of PNA+- and LCA+- antigen-presenting cells pointed to an elevated immune reactivity of lymphoid clusters. This study on the distribution of antigen-presenting cells contributes to a deeper understanding of the structure of lymphoid tissue associated with serous membranes, as well as fat-associated lymphoid aggregates, and underscores the connection between innate and adaptive immunity in the abdominal cavity