Combined heterogeneity in cell size and deformability promotes cancer invasiveness.

Phenotypic heterogeneity is increasingly acknowledged to confer several advantages to cancer progression and drug resistance. Here, we probe the collective importance of heterogeneity in cell size and deformability in breast cancer invasion. A computational model of invasion of a heterogeneous cell aggregate predicts that combined heterogeneity in cell size and deformability enhances invasiveness of the whole population, with maximum invasiveness at intermediate cell-cell adhesion. We then show that small cells of varying deformability, a subpopulation predicted to be enriched at the invasive front, exhibit considerable overlap with the biophysical properties of cancer stem cells (CSCs). In MDA-MB-231 cells, these include CD44 hi CD24- mesenchymal CSCs, which are small and soft, and CD44 hi CD24+ hybrid CSCs, which exhibit a wide range of size and deformability. We validate our predictions by tracking the pattern of cell invasion from spheroids implanted in three-dimensional collagen gels, wherein we show temporal enrichment of CD44 hi cells at the invasive front. Collectively, our results illustrate the advantages imparted by biophysical heterogeneity in enhancing cancer invasiveness.This article has an associated First Person interview with the first author of the paper.

UV-to-NIR Harvesting Conjugated Porous Polymer Nanocomposite: Upconversion and Plasmon Expedited Thioether Photooxidation.

Photocatalysts capable of harvesting a broad range of the solar spectrum are essential for sustainable chemical transformations and environmental remediation. Herein, we have integrated NIR-absorbing upconversion nanoparticles (UCNP) with UV-Vis absorbing conjugated porous organic polymer (POP) through the in situ multicomponent C-C coupling to fabricate a UC-POP nanocomposite. The light-harvesting ability of UC-POP is further augmented by loading plasmonic gold nanoparticles (AuNP) into UC-POP. A three-times enhancement in the upconversion luminescence is observed upon the incorporation of AuNP in UC-POP, subsequently boosting the photocatalytic activity of UC-POP-Au. The spectroscopic and photoelectrochemical investigations infer the enhanced photocatalytic oxidation of thioethers, including mustard gas simulant by UC-POP-Au compared to POP and UC-POP due to the facile electron-hole pair generation, suppressed exciton recombination, and efficient charge carrier migration. Thus, the unique design strategy of combining plasmonic and upconversion nanoparticles with a conjugated porous organic polymer opens up new vistas towards artificial light harvesting.

Tumor promoting role of anti-tumor macrophages in tumor microenvironment.

Recent advances in tumor biology demand detailed analysis of the complex interaction of tumor cells with their adjacent microenvironment (tumor stroma) to understand the various mechanisms involved in tumor growth and metastasis. Mononuclear phagocytes or macrophages, a type of innate immune cells, defend the organism against infection and injury. On the otherhand, tumor associated macrophages (TAMs) constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. Clinical and experimental evidences have shown that cancer tissues with high infiltration of TAMs are associated with poor patient prognosis and resistance to therapies, thus, targeting of TAMs in tumors is considered as a promising immunotherapeutic strategy. Depletion of M2 TAMs or 're-education' of them as anti-tumor effectors might contribute significantly to the search of new modalities in anti-cancer treatments. Basic questions on the factors responsible for homing of macrophages in tumors, mechanism of conversion of M1 to M2 TAMs, their functionality and, finally, the possible ways to target M2 TAMs are discussed.

Differences in Health Care Needs, Health Care Utilization, and Health Care Outcomes Among Children With Special Health Care Needs in Ohio: A Comparative Analysis Between Medicaid and Private Insurance.

OBJECTIVE: This study explores comparative differentials in health care needs, health care utilization, and health status between Medicaid and private/employer-sponsored insurance (ESI) among a statewide population of children with special health care needs (CSHCN) in Ohio. METHODS: We used data from the 2012 Ohio Medicaid Assessment Survey to examine CSHCN's health care needs, utilization, status, and health outcomes by insurance type. Adjusted multivariable logistic regression models were used to explore associations between public and private health insurance, as well as the utilization and health outcome variables. RESULTS: Bivariate analyses indicate that the Medicaid population had higher care coordination needs (odds ratio [OR] = 1.6; 95% confidence interval [CI], 1.1-2.2) as well as need for mental/educational health care services (OR = 1.5; 95% CI; 1.1-2.0). They also reported higher unmet dental care needs (OR = 2.2; 95% CI, 1.2-4.0), higher emergency department (ED) utilization (OR = 2.3; 95% CI, 1.7-3.2), and worse overall health (OR = 0.6; 95% CI, 0.4-0.7), oral health (OR = 0.4; 95% CI, 0.3-0.5), and vision health (OR = 0.4; 95% CI, 0.2-0.6). After controlling for demographic variables, CSHCN with Medicaid insurance coverage were more likely to need mental health and education services (adjusted odds ratio [AOR] = 1.8; 95% CI; 1.2-2.6), had significantly more ED visits (AOR = 2.3; 95% CI, 1.5-3.5), and were less likely to have excellent overall health (AOR = 0.64; 95% CI, 0.4-0.9), oral health (AOR = 0.43; 95% CI, 0.3-0.7), and vision health (AOR = 0.38; 95% CI, 0.2-0.6) than those with private insurance/ESI. CONCLUSION: The CSHCN population is a highly vulnerable population. While Ohio's Medicaid provides greater coverage to CSHCN, disparities continue to exist within access and services that Medicaid provides versus the ones provided by private insurance/ESI.

Tumor-associated mesenchymal stem cells inhibit naïve T cell expansion by blocking cysteine export from dendritic cells.

Mesenchymal stem cells (MSCs) represent an important cellular constituent of the tumor microenvironment, which along with tumor cells themselves, serve to regulate protective immune responses in support of progressive disease. We report that tumor MSCs prevent the ability of dendritic cells (DC) to promote naïve CD4(+) and CD8(+) T cell expansion, interferon gamma secretion and cytotoxicity against tumor cells, which are critical to immune-mediated tumor eradication. Notably, tumor MSCs fail to prevent DC-mediated early T cell activation events or the ability of responder T cells to produce IL-2. The immunoregulatory activity of tumor MSCs is IL-10- and STAT3-dependent, with STAT3 repressing DC expression of cystathionase, a critical enzyme that converts methionine-to-cysteine. Under cysteine-deficient priming conditions, naïve T cells exhibit defective cellular metabolism and proliferation. Bioinformatics analyses as well as in vitro observations suggest that STAT3 may directly bind to a GAS-like motif within the cystathionase promoter (-269 to -261) leading to IL-10-STAT3 mediated repression of cystathionase gene transcription. Our collective results provide evidence for a novel mechanism of tumor MSC-mediated T cell inhibition within tumor microenvironment.

Psychosocial Health, e-Health Literacy, and Perceptions of e-Health as Predictors and Moderators of e-Health Use Among Caregivers of Children with Special Healthcare Needs.

OBJECTIVES: In this study, we explored the relationships between the psychosocial health of caregivers of children with special healthcare needs and their e-health use. Additionally, the analysis examined moderating effects of a caregiver's perceptions of e-health and his or her e-health literacy on the associations among four domains of psychosocial health and e-health use. MATERIALS AND METHODS: To date, 313 caregivers of children, 12-18 years of age, with special healthcare needs have been recruited. Covariate-adjusted multivariable regressions determined associations between psychosocial health domains of caregivers and e-health use. E-health literacy and perceptions of e-health were further tested as moderators of the relationship between psychosocial health and e-health use. RESULTS: Among the caregiver population, 31% had problems with social functioning, 36.1% with communication, 43.3% with family relationships, and 46.3% with worrying for their child. After adjusting for demographic variables, e-health use was associated with poorer levels of social functioning, communication, worry, and family relationship. E-health use was also associated with e-health literacy. Perceptions of e-health significantly moderated the relationships among social functioning, communication, and e-health, with the relationship being significantly stronger in caregivers with more positive perceptions of e-health. CONCLUSIONS: Caregivers of children with special healthcare needs have notable levels of psychosocial challenges and those challenges are associated with their e-health resource seeking. Although e-health interventions, including ones that focus on child health education and caregiver support, may be the future of healthcare, a concerted effort is needed to educate caregivers about the benefits of e-health.

Predictors of Health Literacy and Numeracy Concordance Among Adolescents With Special Health Care Needs and Their Parents.

Parent and teen health literacies (HLs) are employed as teens with chronic illnesses transition to health self-management and the adult health system. This study explores the relationships between parent and teen HL. Teens ages 12-18 with chronic conditions and their parents, sampled from a pediatric Medicaid accountable care organization, completed an interview assessing HL and self-reported competence with written and numerical health information. Rates of teen and parent HL, degree of concordance, and the relationship between concordance and teen-reported competence with health materials were measured. Half (52%) of teens had adequate HL, 62% of teens reported competence with written health materials, and 69% reported competence with numerical information. The correlation between parent and teen HL was modest but significant (ϕ = 0.13, p = .03): 47% of parent-teen dyads were concordant for adequate HL, and 10% were concordant for inadequate HL. Adequate teen HL was associated with parental adequate HL and parental education. Discordance was associated with self-reported competence with written material and numerical material. More than half of parent-teen dyads had at least 1 member with less than adequate HL, and parent-teen HL concordance was associated with teen perception of HL. These findings support the consideration of both independent and dyad HL levels in adolescent care.

E-health use in african american internet users: can new tools address old disparities?

OBJECTIVE: Web-based health information may be of particular value among the African American population due to its potential to reduce communication inequalities and empower minority groups. This study explores predictors of e-health behaviors and activities for African American Internet users. MATERIALS AND METHODS: We used the 2010 Pew Internet and American Life Health Tracking Survey to examine sociodemographic and health status predictors of e-health use behaviors among African Americans. E-health use behaviors included searching for e-health information, conducting interactive health-related activities, and tracking health information online. RESULTS: In the African American subsample, 55% (n=395) were at least "occasional" Internet users. Our model suggests that searching for health information online was positively associated with being helped/knowing someone helped by online information (odds ratio [OR]=5.169) and negatively associated with lower income (OR=0.312). Interactive health activities were associated with having a college education (OR=3.264), being 65 years of age or older (OR=0.188), having a family member living with chronic conditions (OR=2.191), having a recent medical crisis (OR=2.863), and being helped/knowing someone helped by online information (OR=8.335). E-tracking behaviors were significantly stronger among African Americans who had health insurance (OR=3.907), were helped/knowing someone helped by online information (OR=4.931), and were social media users (OR=4.799). CONCLUSIONS: Findings suggest significant differences in e-health information-seeking behaviors among African American Internet users-these differences are mostly related to personal and family health concerns and experiences. Targeted online e-health resources and interventions can educate and empower a significant subset of the population.

Pregnancy-related health information-seeking behaviors among rural pregnant women in India: validating the Wilson model in the Indian context.

OBJECTIVES: Understanding health information-seeking behaviors and barriers to care and access among pregnant women can potentially moderate the consistent negative associations between poverty, low levels of literacy, and negative maternal and child health outcomes in India. Our seminal study explores health information needs, health information-seeking behaviors, and perceived information support of low-income pregnant women in rural India. METHODS: Using the Wilson Model of health information-seeking framework, we designed a culturally tailored guided interview to assess information-seeking behaviors and barriers to information seeking among pregnant women. We used a local informant and health care worker to recruit 14 expectant women for two focus group interviews lasting 45 minutes to an hour each. Thirteen other related individuals including husbands, mothers, mothers-in-law, and health care providers were also recruited by hospital counselors for in-depth interviews regarding their pregnant wives/daughters and daughters-in-law. Interviews were transcribed and analyzed by coding the data into thematic categories. RESULTS: The data were coded manually and emerging themes included pregnancy-related knowledge and misconceptions and personal, societal, and structural barriers, as well as risk perceptions and self-efficacy. Lack of access to health care and pregnancy-related health information led participants to rely heavily on information and misconceptions about pregnancy gleaned from elder women, friends, and mothers-in-law and husbands. Doctors and para-medical staff were only consulted during complications. All women faced personal, societal, and structural level barriers, including feelings of shame and embarrassment, fear of repercussion for discussing their pregnancies with their doctors, and inadequate time with their doctors. CONCLUSION: Lack of access and adequate health care information were of primary concern to pregnant women and their families. POLICY IMPLICATIONS: Our study can help inform policies and multi-sectoral approaches that are being taken by the Indian government to reduce maternal and child morbidity and burdens.

Nuclear α-actinin-4 regulates breast cancer invasiveness and EMT.

Epithelial-to-mesenchymal transition (EMT) is a key process where cells lose their adhesion properties and augment their invasive properties. α-Actinin4 (ACTN4) is an actin crosslinking protein that responds to mechanical stimuli and is found to be elevated in breast cancer patients. While ACTN4 has been implicated in regulating cancer invasiveness by modulating cytoskeletal organization, its nuclear functions remain much less explored. Here we address this question by first establishing a correlation between nuclear localization and invasiveness in breast cancer cells. Using cancer databases, we then establish a correlation between ACTN4 expression and EMT in breast cancer. Interestingly, TGFß-induced EMT induction in MCF10A normal mammary epithelial cells leads to increased ACTN4 expression and nuclear enrichment. We then show that ACTN4 knockdown in MDA-MB-231 breast cancer cells, which harbor sizeable fraction of nuclear ACTN4, leads to reduced invasiveness and loss of mesenchymal traits. Similar behavior was observed in knockdown cells expressing K255E ACTN4, which is primarily localized to the cytosol. Together, our findings establish a role for nuclear ACTN4 in regulating invasiveness via modulation of EMT.

N,N'-octyl biphenothiazine and dibenzothiophene dioxide-based soluble porous organic polymer for biphasic photocatalytic hydrogen evolution.

A donor-acceptor-based soluble porous organic polymer (PzDBS) was fabricated using a flexible core composed of N,N'-octyl biphenothiazine and a rigid building unit involving dibenzothiophene dioxide. The soluble porous organic polymer was explored for aqueous-organic biphasic photocatalytic hydrogen evolution, introducing a promising avenue in the domain of porous polymer photocatalysts.

High monocytic MDSC signature predicts multi-drug resistance and cancer relapse in non-Hodgkin lymphoma patients treated with R-CHOP.

Introduction: Non-Hodgkin Lymphoma (NHL) is a heterogeneous lymphoproliferative malignancy with B cell origin. Combinatorial treatment of rituximab, cyclophsphamide, hydroxydaunorubicin, oncovin, prednisone (R-CHOP) is the standard treatment regimen for NHL, yielding a complete remission (CR) rate of 40-50%. Unfortunately, considerable patients undergo relapse after CR or initial treatment, resulting in poor clinical implications. Patient's response to chemotherapy varies widely from static disease to cancer recurrence and later is primarily associated with the development of multi-drug resistance (MDR). The immunosuppressive cells within the tumor microenvironment (TME) have become a crucial target for improving the therapy efficacy. However, a better understanding of their involvement is needed for distinctive response of NHL patients after receiving chemotherapy to design more effective front-line treatment algorithms based on reliable predictive biomarkers. Methods: Peripheral blood from 61 CD20+ NHL patients before and after chemotherapy was utilized for immunophenotyping by flow-cytometry at different phases of treatment. In-vivo and in-vitro doxorubicin (Dox) resistance models were developed with murine Dalton's lymphoma and Jurkat/Raji cell-lines respectively and impact of responsible immune cells on generation of drug resistance was studied by RT-PCR, flow-cytometry and colorimetric assays. Gene silencing, ChIP and western blot were performed to explore the involved signaling pathways. Results: We observed a strong positive correlation between elevated level of CD33+CD11b+CD14+CD15- monocytic MDSCs (M-MDSC) and MDR in NHL relapse cohorts. We executed the role of M-MDSCs in fostering drug resistance phenomenon in doxorubicin-resistant cancer cells in both in-vitro, in-vivo models. Moreover, in-vitro supplementation of MDSCs in murine and human lymphoma culture augments early expression of MDR phenotypes than culture without MDSCs, correlated well with in-vitro drug efflux and tumor progression. We found that MDSC secreted cytokines IL-6, IL-10, IL-1ß are the dominant factors elevating MDR expression in cancer cells, neutralization of MDSC secreted IL-6, IL-10, IL-1ß reversed the MDR trait. Moreover, we identified MDSC secreted IL-6/IL-10/IL-1ß induced STAT1/STAT3/NF-κß signaling axis as a targeted cascade to promote early drug resistance in cancer cells. Conclusion: Our data suggests that screening patients for high titre of M-MDSCs might be considered as a new potential biomarker and treatment modality in overcoming chemo-resistance in NHL patients.

Two-dimensional Covalent Organic Frameworks for Electrochromic Switching.

The electrochromic materials have received immense attention for the fabrication of smart optoelectronic devices. The alteration of the redox states of the electroactive functionalities results in the color change in response to electrochemical potential. Even though transition metal oxides, redox-active small organic molecules, conducting polymers, and metallopolymers are known for electrochromism, advanced materials demonstrating multicolor switching with fast response time and high durability are of increasing demand. Recently, two-dimensional covalent organic frameworks (2D COFs) have been demonstrated as electrochromic materials due to their tunable redox functionalities with highly ordered structure and large specific surface area facilitating fast ion transport. Herein, we have discussed the mechanistic insights of electrochromism in 2D COFs and their structure-property relationship in electrochromic performance. Furthermore, the state-of-the-art knowledge for developing the electrochromic 2D COFs and their potential application in next-generation display devices are highlighted.

UV to NIR multistate electrochromism and electrofluorochromism in dibenzophenazine-arylamine derivatives.

An intriguing case of intramolecular and intervalence charge transfer-driven multistate electrochromism and electrofluorochromism in dibenzophenazin-(phenyl)methanone and arylamine-based redox-active donor-acceptor-donor molecules was elucidated. Tunable absorption from UV to NIR and on-off switching of fluorescence in a single-component all-organic molecular material by a subtle variation of electric potentials were demonstrated.

Neem leaf glycoprotein salvages T cell functions from Myeloid-derived suppressor cells-suppression by altering IL-10/STAT3 axis in melanoma tumor microenvironment.

Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune functions. We have observed that an immunomodulator, neem leaf glycoprotein (NLGP), inhibits tumor-resident MDSCs and enhances antitumor CD8+ T cell immunity. NLGP inhibits the number as well as functions of tumor-resident MDSCs (Gr1±CD11b±) and enhances antitumor CD8± T cell immunity by downregulating arginase 1 and inducible nitric oxide synthase production in MDSCs. Accordingly, decreased T cell anergy and helper to regulatory T cell conversion have been observed in the presence of NLGP, which ultimately augments T cell functions. Mechanistically, NLGP-mediated rectification of T cell suppressive functions of MDSCs was primarily associated with downregulation of the interleukin (IL)-10/signal transducer and activator of transcription 3 (STAT3) signaling axis within the tumor microenvironment, as confirmed by knockdown of STAT3 (by STAT3-siRNA) and using IL-10-/- mice. Thus, NLGP-mediated suppression of MDSC functions in tumor hosts is appeared to be another associated effective mechanism for the eradication of murine melanoma by NLGP.

Neem leaf glycoprotein reverses tumor-induced and age-associated thymic involution to maintain peripheral CD8+ T cell pool.

Aim: As tumor causes atrophy in the thymus to target effector-T cells, this study is aimed to decipher the efficacy of neem leaf glycoprotein (NLGP) in tumor- and age-associated thymic atrophy. Materials & methods: Different thymus parameters were studied using flow cytometry, reverse transcriptase PCR and immunocyto-/histochemistry in murine melanoma and sarcoma models. Results: Longitudinal NLGP therapy in tumor hosts show tumor-reduction along with significant normalization of thymic alterations. NLGP downregulates intrathymic IL-10, which eventually promotes Notch1 to rescue blockade in CD25+CD44+c-Kit+DN2 to CD25+CD44-c-Kit-DN3 transition in T cell maturation and suppress Ikaros/IRF8/Pu.1 to prevent DN2-T to DC differentiation in tumor hosts. The CD5intTCRαßhigh DP3 population was also increased to endorse CD8+ T cell generation. Conclusion: NLGP rescues tumor-induced altered thymic events to generate more effector T cells to restrain tumor.

Neem leaf glycoprotein prevents post-surgical sarcoma recurrence in Swiss mice by differentially regulating cytotoxic T and myeloid-derived suppressor cells.

Post-surgical tumor recurrence is a common problem in cancer treatment. In the present study, the role of neem leaf glycoprotein (NLGP), a novel immunomodulator, in prevention of post-surgical recurrence of solid sarcoma was examined. Data suggest that NLGP prevents tumor recurrence after surgical removal of sarcoma in Swiss mice and increases their tumor-free survival time. In NLGP-treated tumor-free mice, increased cytotoxic CD8+ T cells and a decreased population of suppressor cells, especially myeloid-derived suppressor cells (MDSCs) was observed. NLGP-treated CD8+ T cells showed greater cytotoxicity towards tumor-derived MDSCs and supernatants from the same CD8+ T cell culture caused upregulation of FasR and downregulation of cFLIP in MDSCs. To elucidate the role of CD8+ T cells, specifically in association with the downregulation in MDSCs, CD8+ T cells were depleted in vivo before NLGP immunization in surgically tumor removed mice and tumor recurrence was noted. These mice also exhibited increased MDSCs along with decreased levels of Caspase 3, Caspase 8 and increased cFLIP expression. In conclusion, it can be stated that NLGP, by activating CD8+ T cells, down regulates the proportion of MDSCs. Accordingly, suppressive effects of MDSCs on CD8+ T cells are minimized and optimum immune surveillance in tumor hosts is maintained to eliminate the residual tumor mass appearing during recurrence.

Neem leaf glycoprotein generates superior tumor specific central memory CD8+ T cells than cyclophosphamide that averts post-surgery solid sarcoma recurrence.

The success of cancer vaccines is limited as most of them induce corrupted CD8+ T cell memory populations. We reported earlier that a natural immunomodulator, neem leaf glycoprotein (NLGP), therapeutically restricts tumor growth in a CD8+ T cell-dependent manner. Here, our objective is to study whether memory CD8+ T cell population is generated in sarcoma hosts after therapeutic NLGP treatment and their role in prevention of post-surgery tumor recurrence, in comparison to the immunostimulatory metronomic cyclophosphamide (CTX) treatment. We found that therapeutic NLGP and CTX treatment generates central memory CD8+ T (TCM) cells with characteristic CD44+CD62LhighCCR7highIL-2high phenotypes. But these TCM cells are functionally impaired to prevent re-appearance of tumors along with compromised proliferative, IL-2 secretive and cytotoxic status. This might be due to the presence of tumor load, even a small one in the host, which serves as a persistent source of tumor antigens thereby corrupting the TCM cells so generated. Surgical removal of the persisting tumors from the host restored the functional characteristics of memory CD8+ T cells, preventing tumor recurrence after surgery till end of the experiment. Moreover, we observed that generation of superior TCM cells in NLGP treated surgically removed tumor hosts is related to the activation of Wnt signalling in memory CD8+ T cells with concomitant inhibition of GSK-3ß and stabilisation of ß-catenin, which ultimately activates transcription of Wnt target genes, like, eomesodermin, a signature molecule of CD8+ TCM cells.

The Role of Health Literacy in Predicting Multiple Healthcare Outcomes Among Hispanics in a Nationally Representative Sample: A Comparative Analysis by English Proficiency Levels.

Health literacy (HL) research among Hispanics currently focuses on individuals with limited English proficiency but impacts of HL on healthcare outcomes among other English language proficiency groups is relatively unknown. Regression models assessed associations between HL and healthcare outcomes for Hispanics overall (n = 4013) and for proficiency level sub-populations using the 2007 Pew Hispanic Health Survey. Overall, Hispanics with adequate HL percieved US medical care as "excellent," were more satisfied with their doctor's help, and reported "excellent" overall health. In the sub-population analysis, "excellent" perception of US healthcare was associated with HL among the Spanish and English dominant groups. Among bilinguals, adequate HL was associated with decreased use of traditional medicine. The effect of adequate HL varied within English proficiency groups. HL research that focuses only on Spanish dominant speakers can exclude a substantial percentage of English proficient or bilingual populations who have low HL.

Neem leaf glycoprotein regulates function of tumor associated M2 macrophages in hypoxic tumor core: Critical role of IL-10/STAT3 signaling.

Heterogeneous tumor microenvironment (TME), broadly divided into tumor core and peripheral sub-microenvironments, differentially polarize normal macrophages into a different form known as tumor associated M2 macrophages (M2TAMs) to promote tumor growth. In view of the extensive immune-editing role of NLGP, here, we have observed that NLGP is effective to convert M2TAMs (CD11b+F4/80high) to M1 (CD11b+F4/80low) more prominently in tumor core, along with downregulation of other M2 associated markers, like, ManR, Ym1, Fizz1. High IL-10:IL-12 ratio at tumor core was downregulated in NLGP treated melanoma bearing mice. Decrease in IL-10 by NLGP is again associated with the decrease in hypoxia, as indicated by prominent downregulation of HIF1α and VEGF, particularly at tumor core. Macrophages exposed to hypoxic tumor core lysates in vitro exhibited high IL-10, HIF1α and VEGF expression that was significantly downregulated by NLGP. Further evidences suggest M2TAM to M1 conversion by NLGP is associated with STAT3-regulated IL-10 dependent pathway without affecting the IL-4 dependent one. Such TAM modulatory functions of NLGP might help in the restriction of melanoma growth by increasing the proportion of M1 TAMs in tumor core that helps in prevention of tumor relapse and dissemination of the tumor mass.