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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. Tumor histocultures have been exploited as tools to predict response to cancer therapy. Here the authors report the development and testing of a tumor histoculture platform to study response to immune checkpoint inhibitors in head and neck squamous cell carcinoma.

Aims: The aim of the study was to assess the correlation between body mass index (BMI) and dental caries of 13-15-years-old school children in urban Bangalore and to compare the correlation between BMI and dental decay amongst government and private school children of age group 13-15 years in Bangalore city. Subjects and Methods: A total of 660 students 13-15 years old were inducted in the study. According to these, 330 students from government schools and 330 students from private schools were examined. A specially designed structured questionnaire was used for compilation of data in the survey. BMI for age percentiles was deducted by weight in kilogram divided by height in meter square. Results: Overall a positive correlation was found between Decayed, Missing, and Filled Teeth DMFT and BMI. In government schools, Overweight children had more mean DMFT (1.43) than other BMI categories while in Private schools, At risk of overweight children had more mean DMFT (1.4) than other category of BMI children. Conclusions: A positive correlation was found between DMFT and BMI. In government schools, Overweight children had more mean DMFT than other BMI category while in Private schools, At risk of overweight children had more mean DMFT than other category children.

Background: Many of the contents of cigarette smoke are genotoxic in nature, and consequently, cytogenetic injury seems to be a trustworthy biomarker for deciding the influence of exposure to chromosome damaging agents in smoke. The cytokinesis-block micronucleus assay (CBMN assay) has been proven to be an effectual tool for the study of micronuclei (MN) that will help in estimating the genotoxicity in tobacco users alone which will further help in early cancer detection. Objective: The objective is to find out whether there is pronounced contrast in genotoxicity between tobacco users and nonusers by determining MN number in peripheral blood lymphocytes using CBMN assay. Methodology: MN frequency in peripheral blood lymphocytes was estimated in 5 ml of fresh blood obtained from sixty individuals using tobacco either smoking, chewing, or combination of both and also from thirty individuals with no habit of tobacco use. All were in the age group of 20-40 years. Results: There was a significant increase in genotoxicity in tobacco users when compared to that of nontobacco users. A positive correlation was also obtained between smoking index and MN frequency in the study. Conclusion: Approximation of frequency of MN by CBMN assay can be used to evaluate the genotoxicity present in blood and helps in identifying tobacco users who are at a high risk for the presence of cancer even before the appearance of clinical changes.

Background: Oral health is an effective unit of general health. Dental caries and periodontal diseases are considered to be the major diseases present in modern times. Over the decades, the idea of maintaining effective oral health and interest in oral health prevention measures has diminished; thus increasing the cost of health care. Aims and Objectives: This study aims to estimate the household expenditure on oral health care among people residing in Kerala, India. Materials and Methods: Five hundred participants were surveyed who were residents of Kerala. A self-administered questionnaire that was tested and validated was used to assess the cost of oral health care. Data collected were analyzed using software for IBM SPSS version 23 for Windows (New York, USA). Results: Of 500 people, 37% are men and 63% are women. 100% of people reported using a toothbrush as an oral hygiene aid. 65% of households reported changing toothbrush for 3 months or more, while 35% of families changed for 1 month or less. Significant statistically weak correlation was observed when education, employment, and income were compared to the annual expenditure on dental care. Furthermore, there has been a moderately strong correlation observed between the socio-economic status of families and the annual cost of dental care. Conclusion: People should be aware of preventive oral hygiene aids, and appropriate policies should be formulated which will ultimately result in decreased expenditure on a curative aspect of the dental disease.

BackgroundThe prognosis of ovarian cancer (OvCa) is poor, with a 5-year survival rate in patients of 59.60% (95% CI, 56.06–63.13).1 Personalized treatment regimens could improve treatment outcome and quality of life. We developed the FarcastTM TruTumor Ovarian Cancer histoculture platform to predict response to therapies enabling personalized treatment options for every patient.MethodsFreshly resected OvCa tissue samples (n=10) along with matched blood were collected from consented patients. Tissue explants were generated and distributed into arms and cultured for 72 h. The functional fidelity of immune components was assessed by stimulating these with anti-CD3 (0.01 µg/ml) + Interleukin-2 (IL2, 100 µg/ml), or with Lipopolysaccharides (LPS, 1 µg/ml). Response was characterized through cytokine release assay and flow cytometry (n=3). Tumor cytotoxic response on treatment with Platin (Cisplatin:3.3 µg/ml, or Carboplatin: 37.1 µg/ml) and/or Taxane (Docetaxel:2 µg/ml, or Paclitaxel:2.7 µg/ml), or Nivolumab (132 µg/ml) was evaluated by quantifying the decrease in tumor content and/or increase in the tumor expression of cleaved caspase 3 (CC3).ResultsAt baseline OvCa samples (n=4) exhibited a higher proportion of lymphocytes (79.88±8.05%) than myeloid sub-population, with a high Programmed cell death protein1, PD1+ T-cell population (43.13±11.97%). Baseline immune content in OvCa was lower in comparison to head and neck cancer but similar to renal cell cancer samples. Post-culture explants exhibited preserved tumor morphology with no significant changes across major immune cell sub-populations. Stimulation with anti-CD3+IL2 resulted in notable increase in proliferating (>2.5-fold) and active (>2.8-fold) cytotoxic-T cells across samples. Additionally, anti-CD3+IL2 stimulation led to substantial fold release of Interferon-γ (15.1±7) and Granzyme-B (2.5±1), while LPS stimulation induced higher fold release of Tumor Necrosis Factor-α (11.3±4.6) and Interleukin-10 (5.5±0.8) with respect to control.OvCa cohort (n=7) receiving Platin and Taxane combination treatment, showed variable treatment response with six of the seven samples showing significant decrease in tumor content (p<0.05). The seventh sample that did not show response to combination treatment but exhibited significant fold increase in tumoral CC3 expression (p<0.01) with Cisplatin treatment.Given the high PD1 expression at baseline, we attempted to check efficacy of Nivolumab (n=3). Effective masking of PD1 receptor indicated drug binding to target. Differential T-cell reinvigoration was observed across samples. None of the treated samples, however, exhibited a significant tumor cell cytotoxicity.ConclusionsThe FarcastTM OvCa TruTumor platform facilitates simultaneous investigation with multiple drug treatment regimens enabling personalized treatment decision making for patients.ReferenceMaleki Z, Vali M, Nikbakht HA, Hassanipour S, Kouhi A, Sedighi S, Farokhi R, Ghaem H. Survival rate of ovarian cancer in Asian countries: a systematic review and meta-analysis. BMC cancer 2023;23(1):1–11.Ethics ApprovalThe Institutional Ethics Committee (IEC) from the sample collection centers approved the protocol (protocol # FCB-PROTOCOL-01) and informed consent for participation in the approved study was obtained from every donor.

BackgroundOnly 1–3 % of patients with Head and Neck Squamous Cell Carcinoma (HNSCC) in low- and middle-income countries can afford Nivolumab treatment even though it is approved for recurrent and metastatic disease.1 Low Dose Nivolumab (LDN) has shown similar efficacy compared to Standard Dose Nivolumab (SDN) in renal and lung cancer.2 3 A recent study demonstrated that HNSCC patient sub-cohort treated with chemotherapy (CT) and LDN showed improved progression-free and overall survival compared to sub-cohort treated with CT alone.1 To better understand the added benefit of the combination treatment, it is important to rule out the contribution of CT alone in the responding patients that might not result in a durable response. To address this, we employed the FarcastTM TruTumor, a near native human histoculture platform which can compare multiple treatment response simultaneously for the same patient sample.MethodsFresh surgically resected HNSCC samples (n=20) along with matched blood were collected from consented patients. Thin explants were generated and distributed into arms. These arms were treated in culture with either LDN (7.3 µg/ml) or SDN (132 µg/ml) and CT (Methotrexate (220.8µg/ml)+erlotinib (2.5µg/ml)+celecoxib (0.7µg/ml) or Paclitaxel (2.7µg/ml)+Carboplatin (37.1µg/ml) alone or CT+LDN for 72 hours. The response was evaluated using histopathology, interferon-γ (IFN-g) cytokine release and flow cytometry.ResultsBoth SDN and LDN treatment led to effective masking of Programmed cell death protein 1 (PD1) expression. No significant difference was observed in tumor cytotoxicity response between LDN and SDN in the same samples (n=8). Analysis of immune cell types and activation markers such as CD8+Granzyme-B+, CD8+Ki67+ T cells also showed no significant difference between LDN and SDN treatments. Comparable IFN-g response was observed in 7/8 samples.We next compared response to CT alone or CT+LDN in the same sample (n=12). Ten out of 12 samples did not show a significant difference in tumor content on treatment with CT+LDN compared to CT alone. Five out of these 10 samples showed a significant increase in cleaved caspase expression in tumor, primarily driven by CT treatment. In two samples CT+LDN showed significant drop in tumor content but not in CT or SDN alone, clearly implicating the benefit of combination treatment.ConclusionsThe FarcastTM TruTumor platform thus provides the unique opportunity to identify patients who would truly benefit from treatment with LDN+CT combination. An observational trial is underway to correlate the response observed in our platform with response of the patient in the clinic.ReferencesPatil VM, Noronha V, Menon N, Rai R, Bhattacharjee A, Singh A, Nawale K, Jogdhankar S, Tambe R, Dhumal S, Sawant R, Alone M, Karla D, Peelay Z, Pathak S, Balaji A, Kumar S, Purandare N, Agarwal A, Puranik A, Mahajan A, Janu A, Kumar Singh G, Mittal N, Yadav S, Banavali S, Prabhash K. Low-dose immunotherapy in head and neck cancer: A randomized study. J Clin Oncol. 2023;41(2):222–232Zhao JJ, Kumarakulasinghe NB, Muthu V, Lee M, Walsh R, Low JL, Choo J, Tan HL, Chong WQ, Ang Y, et al. Low-dose Nivolumab in renal cell carcinoma: A real-world experience. 2021;99(3):192–202Yoo SH, Keam B, Kim M, Kim SH, Kim YJ, Kim TM, Kim DW, Lee JS, Heo DS. Low-dose nivolumab can be effective in non-small cell lung cancer: alternative option for financial toxicity. ESMO Open. 2018;3(5):e000332Ethics ApprovalThe Institutional Ethics Committee (IEC) from the sample collection centers approved the protocol (protocol # FCB-PROTOCOL-01) and informed consent for participation in the approved study was obtained from every donor.

Background: Oral health is an effective unit of general health. Dental caries and periodontal diseases are considered to be the major diseases present in modern times. Over the decades, the idea of maintaining effective oral health and interest in oral health prevention measures has diminished; thus increasing the cost of health care. Aims and Objectives: This study aims to estimate the household expenditure on oral health care among people residing in Kerala, India. Materials and Methods: Five hundred participants were surveyed who were residents of Kerala. A self-administered questionnaire that was tested and validated was used to assess the cost of oral health care. Data collected were analyzed using software for IBM SPSS version 23 for Windows (New York, USA). Results: Of 500 people, 37% are men and 63% are women. 100% of people reported using a toothbrush as an oral hygiene aid. 65% of households reported changing toothbrush for 3 months or more, while 35% of families changed for 1 month or less. Significant statistically weak correlation was observed when education, employment, and income were compared to the annual expenditure on dental care. Furthermore, there has been a moderately strong correlation observed between the socio-economic status of families and the annual cost of dental care. Conclusion: People should be aware of preventive oral hygiene aids, and appropriate policies should be formulated which will ultimately result in decreased expenditure on a curative aspect of the dental disease.

Background: Many of the contents of cigarette smoke are genotoxic in nature, and consequently, cytogenetic injury seems to be a trustworthy biomarker for deciding the influence of exposure to chromosome damaging agents in smoke. The cytokinesis-block micronucleus assay (CBMN assay) has been proven to be an effectual tool for the study of micronuclei (MN) that will help in estimating the genotoxicity in tobacco users alone which will further help in early cancer detection. Objective: The objective is to find out whether there is pronounced contrast in genotoxicity between tobacco users and nonusers by determining MN number in peripheral blood lymphocytes using CBMN assay. Methodology: MN frequency in peripheral blood lymphocytes was estimated in 5 ml of fresh blood obtained from sixty individuals using tobacco either smoking, chewing, or combination of both and also from thirty individuals with no habit of tobacco use. All were in the age group of 20-40 years. Results: There was a significant increase in genotoxicity in tobacco users when compared to that of nontobacco users. A positive correlation was also obtained between smoking index and MN frequency in the study. Conclusion: Approximation of frequency of MN by CBMN assay can be used to evaluate the genotoxicity present in blood and helps in identifying tobacco users who are at a high risk for the presence of cancer even before the appearance of clinical changes.

Aims: The aim of the study was to assess the correlation between body mass index (BMI) and dental caries of 13-15-years-old school children in urban Bangalore and to compare the correlation between BMI and dental decay amongst government and private school children of age group 13-15 years in Bangalore city. Subjects and Methods: A total of 660 students 13-15 years old were inducted in the study. According to these, 330 students from government schools and 330 students from private schools were examined. A specially designed structured questionnaire was used for compilation of data in the survey. BMI for age percentiles was deducted by weight in kilogram divided by height in meter square. Results: Overall a positive correlation was found between Decayed, Missing, and Filled Teeth DMFT and BMI. In government schools, Overweight children had more mean DMFT (1.43) than other BMI categories while in Private schools, At risk of overweight children had more mean DMFT (1.4) than other category of BMI children. Conclusions: A positive correlation was found between DMFT and BMI. In government schools, Overweight children had more mean DMFT than other BMI category while in Private schools, At risk of overweight children had more mean DMFT than other category children.

BackgroundColorectal cancer (CRC) is a significant global health issue. Response rate to immune checkpoint inhibitors (ICI) in MSI-H CRC patients have been encouraging but highly variable, pointing to the need for a better response biomarker for patient selection. We employed the Farcast CRC TruTumor histoculture platform to understand the role and response of immune cell types in the complex Tumor MicroEnvironment (TME) that could identify ICI therapy responders more accurately.MethodsFreshly 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 with media replenished every 24h. The response to T-cell 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.ResultsThe CRC TME (n=6) was compared with other indications, namely, Head and Neck Carcinoma (HNSCC: n=10), Renal Cell Carcinoma (RCC: n=10) and Breast Carcinoma (CaBr: n=10). Though the proportion of effector cell populations like (Cytotoxic T-cells (CD8+), Natural killer T cells (CD3+CD56+) and Natural killer cells (CD3-CD56+)) were present in CRC, the activated effector cell (Granzyme B+; GZMB+) proportions were significantly lower. Interestingly, the proportion of Natural Killer (NK) and NK T-cell proportions were higher in CRC and RCC than the other two indications. Additionally, macrophages were biased towards M2 like in CRC compared to other indications. Upon stimulating the tumor fragments with anti-CD3+IL2, CRC samples (n=5) showed only modest increase in the activation (mean value <10%) which was significantly lower (p<0.05) than the other 3 indications.Despite presence of comparable proportions of exhausted CTL population (CD8+PD1+); the target for nivolumab, in CRC (n=4), RCC (n=2) and CaBr (n=3), Nivolumab treatment induced increase in proportion of activated effector immune cells was much more robust in RCC and CaBr compared to CRC. Of the 4 CRC samples treated with nivolumab 2 (S2 and S4) showed more than 1.1-fold increase in GZMB release. Of the two, in S4 there was 3.7-fold increase in IFN-γ secretion with 1.6-fold increase in Perforin release without exhibiting treatment driven tumor cytotoxicity.ConclusionsThe TruTumor platform reproduced the immunosuppressive TME in CRC and points to the presence of dysfunctional or irreversibly exhausted CTLs that restricts the efficacy of ICI monotherapy. It also provides the opportunity to explore combination therapy strategies to overcome the shortcoming of ICI monotherapy for better outcomes.Ethics ApprovalDonor tissue specimens along with matched blood sample were obtained from consented patients. Institutional Ethics Committee (IEC) from the sample collection centers approved the protocol (protocol # FCB-PROTOCOL-01) and informed consent for participation in the approved study was obtained from every donor.