Treatments targeting TIGIT have gained a lot of attention due to strong preclinical and early clinical results, particularly with anti-PD-(L)1 therapeutics. However, this combination has failed to meet progression-free survival endpoints in phase III trials. Most of our understanding of TIGIT comes from studies of T cell function. Yet, this inhibitory receptor is often upregulated to the same, or higher, extent on NK cells in cancers. Studies in murine models have demonstrated that TIGIT inhibits NK cells and promotes exhaustion, with its effects on tumor control also being dependent on NK cells. However, there are limited studies assessing the role of TIGIT on the function of human NK cells (hNK), particularly in lung cancer. Most studies used NK cell lines or tested TIGIT blockade to reactivate exhausted cells obtained from cancer patients. For therapeutic advancement, a better understanding of TIGIT in the context of activated hNK cells is crucial, which is different than exhausted NK cells, and critical in the context of adoptive NK cell therapeutics that may be combined with TIGIT blockade. In this study, the effect of TIGIT blockade on the anti-tumor activities of human ex vivo-expanded NK cells was evaluated in vitro in the context of lung cancer. TIGIT expression was higher on activated and/or expanded NK cells compared to resting NK cells. More TIGIT+ NK cells expressed major activating receptors and exerted anti-tumor response as compared to TIGIT− cells, indicating that NK cells with greater anti-tumor function express more TIGIT. However, long-term TIGIT engagement upon exposure to PVR+ tumors downregulated the cytotoxic function of expanded NK cells while the inclusion of TIGIT blockade increased cytotoxicity, restored the effector functions against PVR-positive targets, and upregulated immune inflammation-related gene sets. These combined results indicate that TIGIT blockade can preserve the activation state of NK cells during exposure to PVR+ tumors. These results support the notion that a functional NK cell compartment is critical for anti-tumor response and anti-TIGIT/adoptive NK cell combinations have the potential to improve outcomes.

Background: The concept of stigma has been widely used to understand patterns of discrimination and negative ideas surrounding people with mental health problems, yet we know little of the specific nuances of how this might operate beyond the ‘Global North’. Aim: This paper aims to explore the notion of stigma in an Indian context by considering the lived experience of patients, carers and community members. Methods: A sample of 204 participants, representing mental health patients, informal carers and community members was recruited from urban and rural areas in Kerala, India. Participants took part in interviews where they were encouraged to talk about their experiences of mental ill health, attitudes towards these problems, barriers encountered and sources of support. Results: Experiences akin to the experience of stigma in Europe and the United States were elicited but there were important local dimensions specific to the Indian context. The difficulties faced by people with diagnoses of mental disorders in finding marriage partners was seen as an important problem, leading to marriage proposals being refused in some cases, and secrecy on the part of those with mental health problems. Rather than the ‘self-stigma’ identified in the US, participants were more likely to see this as a collective problem in that it could reflect badly on the family group as a whole rather than just the sufferer. Conclusions: In the Indian context, the idioms of stigma emphasised impairments in marriage eligibility and the implications for the family group rather than just the self.

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Background: Mullerian anomalies-developmental anomalies of the mullerian system might involve the uterus, cervix, fallopian tubes and vagina of which anomalies of the uterus are the most common. They are often regarded as a treatable form of infertility and have a prevalence of 0.5% in the general population. Though most of them remain asymptomatic, they contribute a good proportion of recurrent pregnancy losses, obstetric complications and infertility. Their timely diagnosis, management and evaluation of associated anomalies proves to be necessary.Methods: A prospective observational study was undertaken at KIMS, Hubli from 2014 to 2018. The study involved those women who were admitted in the department of obstetrics and gynecology at KIMS, Hubli for various reasons and were detected to have a mullerian anomaly. Their mode of presentation, method of detection, associated anomalies were analysed and statistical conclusions drawn from the same.Results: During the study period of 5 years, a total of 85 cases of mullerian anomalies were detected amounting to an incidence of 0.15%. 35% of them were asymptomatic, infertility (24%) being the next common mode of presentation. Septate/sub-septate uterus was found to have the poorest obstetric outcome. Mullerian anomalies were seen in combination in 14% of the cases and had an association with other anomalies like renal anomalies in 10% of the cases. Surgical correction was done for most of the cases of vaginal septum and septate/sub-septate uterus.Conclusions: Mullerian anomalies are often regarded as an uncommon but treatable form of infertility. Their timely detection, treatment and watchful obstetric management is in need.