Dr. M S Ganesh

Description:Immune checkpoint inhibition (ICI) holds great promise for triple-negative breast cancer (TNBC), while it shows limited response hormone receptor positive (ER/PR+) breast cancer (CaBr). We employed the Farcast CaBr TruTumor histoculture platform, that preserves the native tumor microenvironment (TME), to study the role of tumor resident immune cell types in determining T cell activation levels on ICI treatment, in the two CaBr sub-types. Freshly resected tumor tissue samples along with matched blood were collected from consented patients. Tumor explants were generated and distributed into arms and cultured for 72 h. Media was replenished every 24 h and the supernatant was stored. The response to stimulation with anti-CD3 (100 ng/mL) + Interleukin-2 (IL-2, 100 IU/mL) and treatment with Nivolumab (132 µg/mL) was evaluated using cytokine release and flow cytometry based immune profiling. CaBr (n=115) samples had lower immune component than head and neck squamous cell carcinoma (n=113) (p<0.0001) but similar to ovarian (n=21) and renal cell (n=52) cancer prior to treatment with ICI. Amongst the two sub-types, immune component in TNBC (n=43) was higher than ER/PR+ subtypes (n=46) (p<0.05). TNBC (n=10) showed a greater proportion of lymphocyte (58.46%) compared to myeloid (39.21%) compartment. This bias was not observed in ER/PR+ samples (n=12). Anti-CD3+IL2 stimulation showed similar response between the two CaBr sub-types. Upon treatment with Nivolumab, 2 out of 4 TNBC samples exhibited a response phenotype, with >1.6-fold increase in CD8+GzmB+ cells and interferon-gamma (IFN-γ) release. In contrast, only 1 out of 4 ER/PR+ CaBr samples showed a modest increase of 1.3 fold for CD8+GzmB+ cells with no detectable IFN-γ release. To understand the basis for the differential response in the two sub-types, we studied in detail, one ER/PR+ (H1) and two TNBC (T1 and T2) samples, displaying varying levels of response. T2 and H1 did not show a Nivolumab response phenotype, whereas T1 demonstrated a strong T-cell reinvigoration and tumor cytotoxicity. Interestingly, all three samples showed anti-CD3+IL2 stimulation driven T cell response. tSNE analysis of CTLs in the control arm showed two distinct sub-populations of exhausted CTLs (CD8+PD1+). Population1 (Pop1) was Granzyme B-positive, while population2 (Pop2) was not. Upon anti-CD3 stimulation, Pop1 showed further increase of activation whereas Pop2 did not, indicative of Pop2 being an irreversibly exhausted T cell population. T2 notably had lower Pop1 and Pop2 CTLs, along with highest proportion of monocytes across all three samples pointing towards an immunosuppressive TME. H1 mainly contained over-exhausted Pop2 and negligible Pop1 CTLs. Interplay between different TME immune sub-types, thus influence response to Nivolumab in CaBr. This is effectively captured by the TruTumor platform. Citation Format Mouniss MM, Biswajit Das, Kowshik Jaganathan, Syamkumar V, Moumita Nath, Chandan Bhowal, Dharanidharan M, Saikrishna S, Abdul Haseeb, Pallavi R, Kubera Chandran, Rajashekar M, Oliyarasi M, Méhul Kapur, Jayaprakash C, Venkatesh T, Ganesh MS, Amritha Prabha, Prakash BV, Ravi Krishnappa, Upendra K, Ritu Malhotra, Govindaraj K, Pavithira ., Mohit Malhotra, Nandini Pal Basak, Satish Sankaran. Differential T cell response to anti-PD1 in breast cancer Sub-types is driven by activity of intra-tumoral immune cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5807.

Description:Background Intussusception in adults is a rare condition characterized by a low incidence, which complicates the establishment of standardized management protocols unlike those readily available for pediatric cases. This study presents a case series from our institution alongside a systematic review of existing literature. The objective is to delineate effective management strategies for adult intussusception. Methods A systematic search of databases was conducted covering the period from January 2000 to May 2024. The study focused on adult patients diagnosed with intussusception either pre-operatively or intraoperatively and managed with either surgical intervention or conservative methods. The analysis also included retrospective review of patient records from our institution, specifically targeting individuals over 18 years of age, to determine the predominant types of intussusception and identify any pathological lead points associated with these cases. Results In our study, a total of 1,902 patients were included from 59 selected articles, with a mean age of 52.13 ± 14.95 years. Among them, 1,920 intussusceptions were diagnosed, with 98.3% of cases identified preoperatively. Computed tomography (CT) scan was the primary diagnostic modality used in 88.5% of cases. Abdominal pain was the predominant presenting symptom, observed in 86.23% of cases. Only 29 out of 1,920 cases underwent attempted reduction, while the majority required surgical resection due to the high incidence of malignancy in adult cases. The most common type of intussusception identified was colocolic (16.82%), followed by enteric (13.28%), ileocolic (4.89%), and ileocaecal (0.78%) types. A pathological lead point was observed in 302 out of 673 patients (44.84%), with a notably higher frequency of malignancy associated with colocolic intussusception. Conclusion Surgical management remains the cornerstone in treating adult intussusception, particularly in cases involving the colocolic type, where there is a significant risk of underlying malignancy. Attempts at reduction are generally avoided due to the potential risk of tumor dissemination, which could adversely impact patient outcomes. Contrast-enhanced computed tomography (CECT) of the abdomen is pivotal for accurately diagnosing intussusceptions and guiding appropriate management strategies. It is imperative to adhere strictly to oncological principles during surgical interventions to ensure optimal patient care and outcomes.

Description:Dynamic interactions within the tumor micro-environment drive patient response to immune checkpoint inhibitors. Existing preclinical models lack true representation of this complexity. Using a Head and Neck cancer patient derived TruTumor histoculture platform, the response spectrum of 70 patients to anti-PD1 treatment is investigated in this study. With a subset of 55 patient samples, multiple assays to characterize T-cell reinvigoration and tumor cytotoxicity are performed. Based on levels of these two response parameters, patients are stratified into five sub-cohorts, with the best responder and non-responder sub-cohorts falling at extreme ends of the spectrum. The responder sub-cohort exhibits high T-cell reinvigoration, high tumor cytotoxicity with T-cells homing into the tumor upon treatment whereas immune suppression and tumor progression pathways are pre-dominant in the non-responders. Some moderate responders benefit from combination of anti-CTLA4 with anti-PD1, which is evident from better cytotoxic T-cell: T-regulatory cell ratio and enhancement of tumor cytotoxicity. Baseline and on-treatment gene expression signatures from this study stratify responders and non-responders in unrelated clinical datasets.

Description:Purpose: Marjolins ulcer is a malignant transformation that arises from chronic ulcers or previously traumatized scar that occur usually after burns. To study the clinicopathological characteristics and treatment outcomes of Marjolins ulcer at our institute. Materials and methods: Retrospective analysis of all Marjolins ulcer patients presented to our department from 2018 to 2021 was done. A total of 27 patients of all age groups were included in the study. All the information regarding the diagnosis, treatment and outcome details were collected and analysed.Results: Most of the patients were in the 5th decade of life with an overall male preponderance. The most common cause for Marjolin ulcer was Burns Scar. The mean latency period for the development of Marjolins ulcer was 11 years. Squamous cell carcinoma was the most common histological subtype. 18.5% patients received Adjuvant radiotherapy. At the median follow up of 14 months, one patient presented with locoregional relapse.Conclusion: Chronic non-ulcers that do not respond to treatment should be carefully examined by multidisciplinary team for malignant transformation. Surgery is the mainstay of treatment and Adjuvant Radiotherapy should be considered in high-risk cases to reduce locoregional recurrence. Tumour size and nodal involvement are the main predictors of locoregional relapse.

Description:Purpose: Marjolins ulcer is a malignant transformation arising from chronic ulcers or previously traumatized scars that occur usually after burns. This article aims to study the clinicopathological profile and treatment patterns of Marjolins ulcer. Materials and Methods: Retrospective analysis of all Marjolins ulcer patients presented to Vydehi Cancer Centre from 2018 to 2021 was done. A total of 27 patients of all age groups were included in the study. All information regarding detailed history, clinical examination, treatment details were retrospectively collected and analysed. Results: Most of the patients were in the 5th decade of life with an overall male preponderance. The most common cause for Marjolins ulcer was Burns scars followed by Trauma. Lower extremities were found to be the most predominant site. The mean latency period for the development of Marjolins ulcer was 11 years. Squamous cell carcinoma was the most common histological subtype, Adjuvant Radiotherapy was given to the patients with high-risk features. Conclusion: Chronic non-healing ulcers that do not respond to treatment should be carefully examined for malignant transformation. Surgery is the mainstay of treatment and Adjuvant Radiotherapy should be considered in high-risk cases to reduce locoregional recurrence.