Individual, interpersonal, and organisational factors associated with discrimination in medical decisions affecting people with a migration background with mental health problems: the case of general practice.

OBJECTIVES: Although people with a migration background (MB) have more unmet mental health needs than the general population, patients with a MB are still underrepresented in mental health care services. Provider bias towards these patients has been evidenced repeatedly but its driving factors remain elusive. We assessed the moderating effect of the individual (e.g. age and ethnicity), interpersonal (e.g. healthcare provider trust), and organisational (e.g. perceived workload) factors on general practitioners (GPs) differential decision-making regarding diagnosis, treatment, and referral for a depressed patient with or without a MB. DESIGN: An experimental study was carried out in which GPs were shown one of two video vignettes featuring adult male depressed patients, one with a MB and the other without. Belgian GPs (n = 797, response rate was 13%) had to decide on their diagnosis, treatment, and referral. Analysis of variance and logistic regression were used to analyse the effect of a MB, adding interaction terms for the explanatory variables. RESULTS: Overall, we found that there were ethnic differences in GPs' decisions regarding diagnosis and treatment recommendations. GPs perceived the symptoms of the patient with a MB as less severe (F = 7.68, p < 0.01) and demonstrated a reduced likelihood to prescribe a combination of medical and non-medical treatments (F = 11.55, p < 0.001). Those differences increased in accordance with the GP's age and perceived workload; at an interpersonal level, we found that differences increased when the GP thought the patient was exaggerating his distress. CONCLUSION: This paper showed that lower levels of trust among GPs' towards their migrant patients and high GP workloads contribute to an increased ethnic bias in medical decision-making. This may perpetuate ethnic inequalities in mental health care. Future researchers should develop an intervention to decrease the ethnic inequities in mental health care by addressing GPs' trust in their migrant and ethnic minority patients.

Unintentional Discrimination Against Patients with a Migration Background by General Practitioners in Mental Health Management: An Experimental Study.

Populations with a migration background have a higher prevalence of mental health problems than their native counterparts. They are also more likely to have unmet medical needs and are less frequently referred to mental health services. One potential explanation for this is that physicians, such as general practitioners (GPs), may unintentionally discriminate against migrant patients, particularly when they lack humanization. To date, no experimental study has investigated this hypothesis. This paper assesses the influence of humanization on GPs' discriminatory decisions regarding migrant patients with depression. A balanced 2 × 2 factorial experiment was carried out with Belgian GPs (N = 797) who received video-vignettes depicting either a native patient or a migrant patient with depression. Half of the respondents were exposed to a text that humanized the patient by providing more details about the patient's life story. Decisions related to diagnosis, treatment and referral were collected, as well as the time spent on each video and text, and were analysed using ANOVA. Migrant patients' symptoms were judged to be less severe than those of native patients (F = 7.71, p < 0.05). For almost all treatments, the decision was less favourable for the migrant patient. Humanization had little effect on medical decisions. We observed that GPs spent significantly more time on the vignette with the humanization intervention, especially for the migrant patients. The results indicate that ethnic differences in the management of depression persist in primary care. Humanization, however, does not mitigate those differences in medical decisions.

"Whatever you do, just don't let him notice you're a woman!" General beliefs on women's gender ideology as a function of topic in mixed-gender negotiations.

How one approaches gender differences in general likely influences the way one handles mixed-gender negotiations. In the present paper, we examine general beliefs on how women negotiators do-as opposed to how they "should"-handle gender in order to increase their chances of success. First, we hypothesised that people's general beliefs would support a sexblindness ideology according to which gender is, and indeed should be, ignored in order to succeed. Second, because negotiation comes across as a stereotypically masculine activity, we predicted that prescriptions regarding what women should do to succeed would commonly favour assimilationism (the belief that women need to assimilate to male norms) over sexawareness (the belief that gender differences should be acknowledged and celebrated). We nevertheless predicted a general belief that women might stay away from these prescriptions and rely more on their gender (i.e. endorse sexawareness over assimilationism) within feminine as compared to masculine and neutral-topic negotiations. Together, our two experiments confirm these predictions. We discuss our results in terms of the consequences on women's gender ideology-based strategies, a potentially relevant aspect to their actual negotiating outcomes.

Self-dehumanisation in severe alcohol use disorder: Links with self-stigma and environmental satisfaction.

Metadehumanisation (i.e., the perception of being considered as less than human by others) is proposed to be widespread in stigmatised populations, such as people with severe alcohol use disorder (SAUD). However, the relations between metadehumanisation, self-dehumanisation (i.e., the self-perception of being less than human), and stigmatisation (i.e., the negative taint applied to some groups) remain unexplored. The aim of this research is thus to investigate the relations between these processes. Metadehumanisation, self-dehumanisation, self-stigma (and its subdimensions) and environmental satisfaction were assessed in 120 inpatients with SAUD and analysed in a mediational model. Stigma awareness was positively associated with metadehumanisation, whereas environmental satisfaction was negatively associated with metadehumanisation. Stigma's application to the self was associated with increased self-dehumanisation. Self-stigma and self-dehumanisation are closely intertwined phenomena. Self-dehumanisation seems to follow a multi-step process suggesting that some steps, such as dehumanisation awareness, are missing from current models of dehumanisation.

Two Preregistered Direct Replications of "Objects Don't Object: Evidence That Self-Objectification Disrupts Women's Social Activism".

Self-objectification has been claimed to induce numerous detrimental consequences for women at the individual level (e.g., sexual dysfunction, depression, eating disorders). Additionally, at the collective level, it has been proposed that self-objectified women might themselves contribute to the maintenance of the patriarchal status quo, for instance, by participating less in collective action. In 2013, Calogero found a negative link between self-objectification and collective action, which was mediated by the adoption of gender-specific system justification. Here, we report two preregistered direct replications (PDRs) of Calogero's original study. We conducted these PDRs after three failures to replicate the positive relation between self-objectification and gender-specific system-justification belief in correlational studies. Results of the two PDRs, in which we used a Bayesian approach, supported the null hypothesis. This work has important theoretical implications because it challenges the role attributed to self-objectified women in the maintenance of patriarchy.

Carcinogenic HPV infection in the cervical squamo-columnar junction.

Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and advanced (squamous cell and adeno-carcinomas) cervical neoplasia. However, there is little evidence to date showing that SCJ cells harbour carcinogenic HPV or are instrumental in the initial phases of neoplasia. This study was designed to (1) determine if normal-appearing SCJ cells contained evidence of carcinogenic HPV infection and (2) trace their transition to early SIL. Sections of cervix from high-risk reproductive age women were selected and SCJ cells were analysed by using several techniques which increasingly implicated HPV infection: HPV DNA (genotyping and in situ hybridization)/RNA (PCR), immunostaining for HPV16 E2 (an early marker of HPV infection), p16(ink4), Ki67, and HPV L1 protein. In 22 cases with a history of SIL and no evidence of preneoplastic lesion in the excision specimen, HPV DNA was isolated from eight of ten with visible SCJ cells, six of which were HPV16/18 DNA-positive. In five of these latter cases, the SCJ cells were positive for p16(ink4) and/or HPV E2. Transcriptionally active HPV infection (E6/E7 mRNAs) was also detected in microdissected SCJ cells. Early squamous atypia associated with the SCJ cells demonstrated in addition diffuse p16(ink4) immunoreactivity, elevated proliferative index, and rare L1 antigen positivity. We present for the first time direct evidence that normal-appearing SCJ cells can be infected by carcinogenic HPV. They initially express HPV E2 and their progression to SIL is heralded by an expanding metaplastic progeny with increased proliferation and p16(ink4) expression. Whether certain SCJs are more vulnerable than others to carcinogenic HPV genotypes and what variables determine transition to high-grade SIL remain unresolved, but the common event appears to be a vulnerable cell at the SCJ.

HMGB1 secretion during cervical carcinogenesis promotes the acquisition of a tolerogenic functionality by plasmacytoid dendritic cells.

Acquisition of an impaired functionality by plasmacytoid dendritic cells (pDCs) contributing to cancer progression has been documented in different types of cancers. In the present study, we postulate that molecules secreted by (pre)neoplastic epithelial cells of the genital tract (cervix/vulva) might attract pDCs but also modify their proper functionality, allowing these cells to initiate a tolerogenic response interfering with antitumor immunity. We demonstrated that pDCs are recruited during the cervical metaplasia-dysplasia-cancer sequence, through the action of their chemoattractant, chemerin. We showed that stimulated-pDCs exposed to cervical/vulvar tumor microenvironment display an altered phenotype. We also demonstrated that cervical/vulvar neoplastic keratinocytes inhibit the proper function of pDCs by decreasing their IFNα secretion in response to CpG oligonucleotides. In parallel, we observed that (pre)neoplastic areas of the cervix are infiltrated by FoxP3(+) Treg cells which colocalize with pDCs. Accordingly, pDCs cocultured with cervical/vulvar neoplastic keratinocytes have the capacity to induce a Treg cell differentiation from naïve CD4(+) T cells, which is in agreement with the development of a tolerogenic response. We identified HMGB1 as a soluble factor produced by neoplastic keratinocytes from the genital tract involved in pDCs functional alteration. Indeed, this molecule inhibited pDC maturation, decreased IFNα secretion following TLR9 stimulation and forced these cells to become tolerogenic. In contrast, inhibition of HMGB1 restored pDC phenotype. Our findings indicate that the use of inhibitory molecules notably directed against HMGB1 in cervical/vulvar (pre)neoplastic lesions might prevent alterations of pDCs functionality and represent an attractive therapeutic strategy to overcome immune tolerance in cancers.

Altered α-defensin 5 expression in cervical squamocolumnar junction: implication in the formation of a viral/tumour-permissive microenvironment.

Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix, which mainly develops at the squamocolumnar (SC) junction. The progression of cervical HPV infections into (pre)neoplastic lesions suggests that viral antigens are not adequately recognized by innate immunity or presented to the adaptive immune system. Members of the defensin family have recently been found to inhibit viral and bacterial pathogens, to stimulate the migration of immune cells and to play a role in anticancer responses. In the present study, we focused on the poorly characterized human α-defensin 5 (HD-5) and its possible role in these processes. We showed that HD-5 was able to prevent HPV virion entry into cervical keratinocytes and to influence adaptive immunity. Indeed, this peptide specifically induced the chemoattraction and proliferation of both activated T lymphocytes and immature dendritic cells in a CCR2/CCR6-dependent manner and stimulated the infiltration of these professional antigen-presenting cells in a (pre)neoplastic epithelium transplanted in vivo in immunodeficient mice. No chemotactic effect was observed with plasmacytoid dendritic cells, macrophages or natural killer cells. Proliferative and angiogenic effects of HD-5 were also assessed in vitro and in vivo. However there was a striking regional disparity in expression of HD-5, being prominent in ectocervical, vaginal and vulvar neoplasia, while absent, or nearly so, in the cervical SC junction. Taken together, these results suggest one possible explanation for why the SC junction is uniquely vulnerable to both high-risk HPV infection (via reduced HD-5 expression and viral entry) and progression of neoplasia (via altered cell-mediated immune responses and altered microenvironment).

Dendritic cells in Barrett's esophagus carcinogenesis: an inadequate microenvironment for antitumor immunity?

Barrett's esophagus corresponds to the replacement of the normal esophageal squamous epithelium by a columnar epithelium through a metaplastic process. This tissue remodeling is associated with chronic gastroesophageal reflux and constitutes a premalignant lesion leading to a 30- to 60-fold increase in the risk to evolve into esophageal adenocarcinoma. The present study aimed to investigate a possible immune evasion in Barrett's esophagus favoring esophageal adenocarcinoma development. We demonstrated that myeloid and plasmacytoid dendritic cells are recruited during the esophageal metaplasia-dysplasia-carcinoma sequence, through the action of their chemoattractants, macrophage inflammatory protein 3α and chemerin. Next, we showed that, in contrast to plasmacytoid dendritic cells, myeloid dendritic cells, co-cultured with Barrett's esophagus and esophageal adenocarcinoma cell lines, display a tolerogenic phenotype. Accordingly, myeloid dendritic cells co-cultured with esophageal adenocarcinoma cell lines stimulated regulatory T cell differentiation from naïve CD4(+) T cells. In agreement with those results, we observed that both metaplastic areas and (pre)malignant lesions of the esophagus are infiltrated by regulatory T cells. In conclusion, soluble factors secreted by epithelial cells during the esophageal metaplasia-dysplasia-carcinoma sequence influence dendritic cell distribution and promote tumor progression by rendering them tolerogenic.

Inherence heuristic versus essentialism: Issues of antecedence and cognitive mechanism.

We argue (1) that the empirical evidence offered by the authors is insufficient to sustain their claim; (2) that, beyond methodological problems, the proposed underlying cognitive mechanism is largely speculative and that a reverse, more motivational, path is equally plausible; and (3) that the distinction and antecedence of inherence intuitions with respect to essentialist beliefs remain to be demonstrated.

Backfire effects of performance quantification on stress and disidentification: The role of metadehumanization in organizations, sport, and social networks.

Quantification, that is, the shaping of human environments in numerical terms, is so widespread in contemporary societies that it has contaminated almost all spheres of human life. We explore the links between performance quantification and individuals' feelings of being treated in a dehumanized way, that is, metadehumanization. We present an integrative research that assessed the relationships between performance quantification, metadehumanization, and on two of metadehumanization's consequences, that is, stress and disidentification, in three contexts, that is, organizations, sport, and social networks. In addition, we test the moderating roles of two individual variables, that is, competitiveness and tender-mindedness, in this model. In three samples (Ns = 204, 300, 297, for Samples A, B, and C, respectively), we show a mediation effect of metadehumanization on the links between performance quantification and stress and disidentification that holds despite of contextual variations. Unexpectedly, our two moderated mediation hypotheses did not hold or showed inconsistent effects across samples.

Suicidal ideations and self-dehumanization in recently detoxified patients with severe alcohol use disorder: an experimental exploration through joint explicit-implicit measures.

BACKGROUND: Metadehumanization (the feeling of being considered as less than human by others) is a pervasive phenomenon in psychiatric states, notably promoting self-dehumanization and suicide antecedents. However, its role in suicidal ideations among patients with addictive disorders remains unexplored. We thus investigated the involvement of metadehumanization/self-dehumanization in suicidal ideations and suicidal thoughts interference in severe alcohol use disorder. METHODS: We measured metadehumanization, suicidal ideations, and desire for social contact through questionnaires among 35 recently detoxified patients with severe alcohol use disorder (26 males). We measured animalistic/mechanistic self-dehumanization using an Implicit Association Task, and suicidal thoughts interference using a Stroop Task with suicide-related words. We performed regression analyses while controlling for depression/anxiety. RESULTS: Animalistic self-dehumanization was positively associated with suicidal thoughts interference and with decreased desire for social interactions, such link being absent for metadehumanization or mechanistic self-dehumanization. CONCLUSIONS: This link between self-dehumanization and suicide-related factors suggests that a reduced sense of belonging to humanity is associated with self-harm antecedents. Results also emphasize the importance of using indirect measures to investigate sensitive variables, such as self-dehumanization and suicidal thoughts.

Implicit and explicit ethnic biases in multicultural primary care: the case of trainee general practitioners.

BACKGROUND: General Practitioners (GPs) are the first point of contact for people from ethnic and migrant groups who have health problems. Discrimination can occur in this health care sector. Few studies, however, have investigated implicit and explicit biases in general practice against ethnic and migrant groups. This study, therefore, investigated the extent of implicit ethnic biases and willingness to adapt care to migrant patients among trainee GPs, and the factors involved therein, in order to measure explicit bias and explore a dimension of cultural competence. METHODS: In 2021, data were collected from 207 trainee GPs in the French-speaking part of Belgium. The respondents passed an Implicit Association Test (IAT), a validated tool used to measure implicit biases against ethnic groups. An explicit attitude of willingness to adapt care to diversity, one of the dimensions of cultural competence, was measured using the Hudelson scale. RESULTS: The overwhelming majority of trainee GPs (82.6%, 95% CI: 0.77 - 0.88) had implicit preferences for their ingroup to the detriment of ethnic and migrant groups. Overall, the majority of respondents considered it the responsibility of GPs to adapt their attitudes and practices to migrants' needs. More than 50% of trainee GPs, however, considered it the responsibility of migrant patients to adapt to the values and habits of the host country. CONCLUSIONS: This study found that the trainee GPs had high to very high levels of implicit ethnic bias and that they were not always willing to adapt care to the values of migrants. We therefore recommend that they are made aware of this bias and we recommend using the IAT and Hudelson scales as educational tools to address ethnic biases in primary care.

Sex-based and beauty-based objectification: Metadehumanization and emotional consequences among victims.

We investigated how two forms of objectification (i.e., sex- and beauty-based objectification) relate to metadehumanization (i.e., the perception of being dehumanized) and emotional consequences for victims. Capitalizing on previous research, we hypothesized that sex-based objectification would induce animalistic metadehumanization and that beauty-based objectification would induce mechanistic metadehumanization. Our four studies showed that sex-based objectification elicits stronger mechanistic metadehumanization than beauty-based objectification, which also elicits higher mechanistic metadehumanization than non-objectifying control condition. Unexpectedly, animalistic metadehumanization did not vary across conditions. These findings suggest that, consistent with the social metaphor, objectified women feel mechanistically dehumanized, independently of the objectification type faced. Sex- and beauty-based objectifications also elicit more anger but less sadness than the control condition. However, only sex-based objectification increases guilt feelings. The general discussion contrasts perpetrators' vision of objectified women to women's own experience of objectification.

My Physical Appearance at the Center of Others' Concerns: What are the Consequences for Women's Metadehumanization and Emotions?

Despite the frequency of women's exposure to sexually objectifying behaviors in their daily life (e.g., through comments on their appearance, gazing or touching), no previous work has investigated how such a focus on their physical appearance influences women's meta-perceptions. Capitalizing on recent studies showing that sexually objectified women are dehumanized by both male and female participants, the present paper investigates women's metadehumanization (i.e., their perceptions of being viewed as less than fully human) and its emotional consequences following interpersonal sexual objectification. In three studies, we showed that when an interaction partner focuses on their physical appearance, women report higher levels of metadehumanization, as well as increased anger and sadness, than when the partner focuses on non-physical parts. Theoretical and empirical contributions of the present findings are discussed.

Dual inhibition of factor XIIa and factor XIa as a therapeutic approach for safe thromboprotection.

Clinical practice shows that a critical unmet need in the field of medical device-associated thrombosis prevention is the availability of an anticoagulant therapy without hemorrhagic risk. In the quest for new drugs that are at least as effective as those currently available, while avoiding bleeding complications, molecules that target nearly every step of the coagulation pathway have been developed. Among these molecules, inhibitors of factor XII (FXII) or factor XI (FXI) are promising alternatives as deficiencies in these factors protect against thrombosis without causing spontaneous hemorrhage, as revealed by epidemiological and preclinical data. Ixodes ricinus-contact phase inhibitor (Ir-CPI), a new anticoagulant candidate with an innovative mechanism of action could be this ideal anticoagulant agent for safe prevention from clotting on medical devices. This protein, which selectively binds to FXIIa, FXIa, and plasma kallikrein and inhibits the reciprocal activation of FXII, prekallikrein, and FXI in human plasma, was shown to prevent thrombosis in an ovine cardiopulmonary bypass system associated with cardiac surgeries. Furthermore, as opposed to unfractionated heparin, Ir-CPI appears to be devoid of bleeding risk. This review outlines the rationale for targeting upstream coagulation factors in order to prevent medical device-associated thrombosis; examines the novel approaches under development; and focuses on Ir-CPI, which shows promising properties in the field of thrombosis prevention.

Metadehumanization and Self-dehumanization are Linked to Reduced Drinking Refusal Self-Efficacy and Increased Anxiety and Depression Symptoms in Patients with Severe Alcohol Use Disorder.

Metadehumanization, the perception of being treated as less than a human by others, is a pervasive phenomenon in intergroup relations. It is dissociated from stigmatization or stereotypes, and it has been recently identified as a critical process in severe alcohol use disorders (SAUD). Metadehumanization is associated with a wide array of negative consequences for the victim, including negative emotions, aversive self-awareness, cognitive deconstruction, and psychosomatic strains, which are related to anxiety and depression. This study aims to investigate if metadehumanization occurring among patients with SAUD is associated with clinical factors involved in the maintenance of the disease, namely symptoms of depression or anxiety and drinking refusal self-efficacy. A cross-sectional study was conducted among 120 patients with SAUD. Self-reported questionnaires measured metadehumanization, self-dehumanization (i.e., the feeling of being less than a human), anxiety, depression, drinking refusal self-efficacy, and demographics. Metadehumanization was significantly associated with self-dehumanization, anxiety, depression, and drinking refusal self-efficacy. Additionally, path analyses showed that self-dehumanization mediated the links between metadehumanization and clinical variables. These results indicate that metadehumanization and self-dehumanization could be essential factors to consider during SAUD treatment, as they are associated with increased psychiatric symptoms and reduced drinking refusal self-efficacy.

Examining the role of fundamental psychological needs in the development of metadehumanization: A multi-population approach.

In the present paper, we investigate dehumanization processes from a victim perspective. We propose that dehumanization experiences, that is metadehumanization, arise from people's feelings that their fundamental human needs are thwarted and that such experiences influence their emotions, self-esteem, and coping strategies. Our model is put at test in three contexts involving different types of dehumanization victims: Women (Study 1a, N = 349), patients with severe alcohol use disorder (Study 1b, N = 120), and employees in organizations (Study 1c, N = 347). Our integrated model of metadehumanization, which considers both its antecedents and consequences, proved stable across contexts and populations and therefore helps building bridges between different psychological disciplines in which dehumanization occurs.

Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy.

BACKGROUND: High-mobility group box 1 (HMGB1) is a multifunctional redox-sensitive protein involved in various intracellular (eg, chromatin remodeling, transcription, autophagy) and extracellular (inflammation, autoimmunity) processes. Regarding its role in cancer development/progression, paradoxical results exist in the literature and it is still unclear whether HMGB1 mainly acts as an oncogene or a tumor suppressor. METHODS: HMGB1 expression was first assessed in tissue specimens (n=359) of invasive breast, lung and cervical cancer and the two distinct staining patterns detected (nuclear vs cytoplasmic) were correlated to the secretion profile of malignant cells, patient outcomes and the presence of infiltrating immune cells within tumor microenvironment. Using several orthotopic, syngeneic mouse models of basal-like breast (4T1, 67NR and EpRas) or non-small cell lung (TC-1) cancer, the efficacy of several HMGB1 inhibitors alone and in combination with immune checkpoint blockade antibodies (anti-PD-1/PD-L1) was then investigated. Isolated from retrieved tumors, 14 immune cell (sub)populations as well as the activation status of antigen-presenting cells were extensively analyzed in each condition. Finally, the redox state of HMGB1 in tumor-extruded fluids and the influence of different forms (oxidized, reduced or disulfide) on both dendritic cell (DC) and plasmacytoid DC (pDC) activation were determined. RESULTS: Associated with an unfavorable prognosis in human patients, we clearly demonstrated that targeting extracellular HMGB1 elicits a profound remodeling of tumor immune microenvironment for efficient cancer therapy. Indeed, without affecting the global number of (CD45+) immune cells, drastic reductions of monocytic/granulocytic myeloid-derived suppressor cells (MDSC) and regulatory T lymphocytes, a higher M1/M2 ratio of macrophages as well as an increased activation of both DC and pDC were continually observed following HMGB1 inhibition. Moreover, blocking HMGB1 improved the efficacy of anti-PD-1 cancer monoimmunotherapy. We also reported that a significant fraction of HMGB1 encountered within cancer microenvironment (interstitial fluids) is oxidized and, in opposite to its reduced isoform, oxidized HMGB1 acts as a tolerogenic signal in a receptor for advanced glycation endproducts-dependent manner. CONCLUSION: Collectively, we present evidence that extracellular HMGB1 blockade may complement first-generation cancer immunotherapies by remobilizing antitumor immune response.

Immune suppression in head and neck cancers: a review.

Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate remained below 50% for the past 30 years. The worse prognosis of these cancers must certainly be link to the fact that HNSCCs strongly influence the host immune system. We present a critical review of our understanding of the HNSCC escape to the antitumor immune response such as a downregulation of HLA class I and/or components of APM. Antitumor responses of HNSCC patients are compromised in the presence of functional defects or apoptosis of T-cells, both circulating and tumor-infiltrating. Langerhans cells are increased in the first steps of the carcinogenesis but decreased in invasive carcinomas. The accumulation of macrophages in the peritumoral areas seems to play a protumoral role by secreting VEGF and stimulating the neoangiogenesis.