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Severe and progressive weight loss is a feature of pancreatic cancer but it has been unclear whether dietetic intervention can improve patient outcomes. This study is a post hoc analysis of the extensive data available from the multicentre BH80 Cancer Cachexia trial to examine how patients with unresectable pancreatic cancer respond to intensive dietetic intervention. The BH80 study compared an n-3 fatty acid enriched oral supplement with an isonitrogenous, isocaloric supplement given over an eight week period. Additional qualitative data was also collected and examined for the patients recruited by the Australian sites. The aims were to determine whether achieving weight stabilisation is an appropriate goal of nutrition intervention for people with unresectable pancreatic cancer; to identify determinants of weight stabilisation; and to describe nutrition-related features of patients recruited by the Australian sites, prior to and during intensive nutrition intervention. Data from 107 patients for whom weight change data over an eight week nutrition intervention period was available, was divided into weight losing (less than 1kg lost) and weight stable (less than or equal to 1 kg lost) patients. Group survival duration (Kaplan Meier log rank test) and global quality of life (EORTC QLQ-C30 global health status/quality of life) were compared. Variables including energy intake, BMI, presence of pain, nausea and vomiting, and appetite loss, C reactive protein and stage of disease were also compared to determine predictors of weight stability using logistic regression analysis. This study demonstrates that weight stabilisation is not only achievable for some patients in the short term, but it is also associated with improved outcomes. Those patients who were able to stabilise their weight after eight weeks of oral nutrition support lived longer from baseline and reported better quality of life than those who continued to lose weight. Weight stabilisation is therefore a reasonable and worthwhile goal for this patient group.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 147-167).

Made available in DSpace on 2014-06-11T19:27:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2006-04-10Bitstream added on 2014-06-13T18:32:19Z : No. of bitstreams: 1 borges_vp_me_jabo.pdf: 810273 bytes, checksum: 0704631ed3d05666adee30a0ec98e496 (MD5) / Universidade Estadual Paulista (UNESP) / A caquexia figura como uma das mais importantes causas de condenação total de frangos de corte durante a inspeção em abatedouros frigoríficos determinando grandes prejuízos ao setor avícola. Para melhor entender esta enfermidade foram estudados os aspectos macro e microscópicos de 400 aves caquéticas de um abatedouro frigorífico sob Inspeção Federal no Estado de Mato Grosso do Sul. Foram relatadas e catalogadas todas as lesões macro e microscópicas das aves caquéticas examinadas. Devido às diferentes alterações detectadas e aos diversos órgãos atingidos pôde-se concluir que as etiologias devem ser variadas. O fígado, sacos aéreos e pele foram os órgãos mais comumente comprometidos. O envolvimento do fígado, em vários graus e com lesões diferenciadas, em grande parcela dos casos induziu à percepção de que o comprometimento deste órgão - importante para a síntese protéica - está intimamente relacionado ao aparecimento de quadros de caquexia. A lesão de degeneração da cabeça femoral, embora não tenha sido uma alteração freqüentemente detectada têm correlação positiva com o aparecimento de casos de nefrite caseosa. O índice de aparecimento de lesões teciduais maior nos animais caquéticos que naqueles não caquéticos e o fato de que períodos curtos de privação alimentar não interferem no aparecimento de graus mais severos de caquexia são dados que corroboram para o entendimento de que esta é uma síndrome associada a enfermidades e não à fome. / Cachexia is one of the most important causes of carcass downgrading in poultry inspection and it determines serious losses to poultry industry. To better understand this syndrome, the macro and microscopic aspects of 400 cachetic carcasses were studied in a slaughterhouse under Federal inspection in Mato Grosso do Sul State. Each macro and microscopic lesion was reported and classified. Because of the several alterations in many viscera it was possible to conclude that there must be a plenty of etiologies. Liver, air sacs and skin were the most compromised organs. Hepatic involvement in different levels induce to the perception that this important organ in protein synthesis is close related to cachexia cases. Femoral head degeneration although not frequently identified showed a positive correlation to caseous nephritis. Ali the studied lesions were greater in cachetic animais when compared to non-caquetic broilers. This data associated to the fact that short periods of time of food deprivation do not interfere in severe cases of cachexia corroborate to the understanding that this is a syndrome related to diseases and not to hunger.

Orientador: Oswaldo Durival Rossi Júnior / Banca: Antonio Carlos Alessi / Banca: Eurípedes Batista Guimarães / Resumo: A caquexia figura como uma das mais importantes causas de condenação total de frangos de corte durante a inspeção em abatedouros frigoríficos determinando grandes prejuízos ao setor avícola. Para melhor entender esta enfermidade foram estudados os aspectos macro e microscópicos de 400 aves caquéticas de um abatedouro frigorífico sob Inspeção Federal no Estado de Mato Grosso do Sul. Foram relatadas e catalogadas todas as lesões macro e microscópicas das aves caquéticas examinadas. Devido às diferentes alterações detectadas e aos diversos órgãos atingidos pôde-se concluir que as etiologias devem ser variadas. O fígado, sacos aéreos e pele foram os órgãos mais comumente comprometidos. O envolvimento do fígado, em vários graus e com lesões diferenciadas, em grande parcela dos casos induziu à percepção de que o comprometimento deste órgão - importante para a síntese protéica - está intimamente relacionado ao aparecimento de quadros de caquexia. A lesão de degeneração da cabeça femoral, embora não tenha sido uma alteração freqüentemente detectada têm correlação positiva com o aparecimento de casos de nefrite caseosa. O índice de aparecimento de lesões teciduais maior nos animais caquéticos que naqueles não caquéticos e o fato de que períodos curtos de privação alimentar não interferem no aparecimento de graus mais severos de caquexia são dados que corroboram para o entendimento de que esta é uma síndrome associada a enfermidades e não à fome. / Abstract: Cachexia is one of the most important causes of carcass downgrading in poultry inspection and it determines serious losses to poultry industry. To better understand this syndrome, the macro and microscopic aspects of 400 cachetic carcasses were studied in a slaughterhouse under Federal inspection in Mato Grosso do Sul State. Each macro and microscopic lesion was reported and classified. Because of the several alterations in many viscera it was possible to conclude that there must be a plenty of etiologies. Liver, air sacs and skin were the most compromised organs. Hepatic involvement in different levels induce to the perception that this important organ in protein synthesis is close related to cachexia cases. Femoral head degeneration although not frequently identified showed a positive correlation to caseous nephritis. Ali the studied lesions were greater in cachetic animais when compared to non-caquetic broilers. This data associated to the fact that short periods of time of food deprivation do not interfere in severe cases of cachexia corroborate to the understanding that this is a syndrome related to diseases and not to hunger. / Mestre

CCAAT/Enhancer Binding Proteins are a family of six bZIP transcription factors. C/EBPβ, the second member cloned, has been implicated in adipogenesis and osteogenesis, but the role of C/EBPβ in myogenesis remained undetermined. In adults, muscle-resident stem cells, called satellite cells (SCs), have the greatest propensity to regenerate the skeletal muscle. We found that C/EBPβ is expressed in SCs, and its expression progressively declines upon differentiation. Forcing the expression of C/EBPβ in myoblasts enhanced the expression of the SC marker Pax7, and repressed MyoD and the myogenic genes expression, resulting in the inhibition of myogenesis. Using a SC-specific conditional knockout (cKO) mouse model, we found that cKO myoblasts have decreased expression of Pax7, and we identified Pax7 as a direct target of C/EBPβ action. In vivo, excision of C/EBPβ resulted in muscle hypertrophy at the juvenile age, and adult cKO animals had enhanced muscle regeneration following BaCl2 muscle injury. Moreover, the number of Pax7+ cells in cKO animals decreased following BaCl2 injury. Upon performing a second injury into cKO animals, we demonstrate a decreased muscle fiber size and an exacerbation of the percentage number of SCs. While cKO animals repaired well a BaCl2 injury, regeneration failed in cKO animals following cardiotoxin (CTX) injury. We demonstrate that IL-1β expression is enhanced in muscle after CTX injury when compared to BaCl2, and we found that IL-1β can stimulate the expression of C/EBPβ in myoblasts. Ectopic C/EBPβ expression can protect myoblasts from apoptosis when triggered with thapsigargin, whereas cKO myoblasts are more sensitive to apoptosis. Using cancer cachexia as a model of chronic inflammation, we found that the expression of C/EBPβ is stimulated in the SCs of cachectic animals, and this correlated with a decrease in regenerative capacity. The severity of muscle wasting was not improved in cKO animals, but rather cKO SCs were lost to apoptosis. Together, this study establishes a protective role for C/EBPβ in muscle SCs in conditions of inflammation.

Orientador: Jose Barreto Campello Carvalheira / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T11:52:05Z (GMT). No. of bitstreams: 1 Pimentel_GustavoDuarte_D.pdf: 5245849 bytes, checksum: ec5c43602ec0d60564455aae4b1fee3a (MD5) Previous issue date: 2015 / Resumo: A teoria das doenças geradas por citocinas inflamatórias trouxe ao longo dos anos indícios que o organismo pode produzir citocinas que desempenham respostas biológicas benéficas ou prejudiciais. Com o passar dos anos ficou claro que a inflamação é um mecanismo chave na fisiopatologia do câncer. Interessantemente, diversos estudos sugerem que a AMPK e mTOR hipotalâmica, importantes moléculas no controle do balanço energética também seja responsável por modular a inflamação e anorexia. Nesse sentido, foi observado: 1) A inibição da AMPK hipotalâmica proporciona redução do peso corporal e da inflamação central e periférica potencializando o crescimento tumoral. Por outro lado, a ativação da AMPK com AICAR, salicilato e vetor viral reverte à anorexia induzida pelo câncer. Entretanto, os efeitos benéficos do AICAR foram bloqueados quando associados com os antagonistas colinérgicos, sugerindo que a AMPK no núcleo ventromedial é responsável pelo controle da anorexia e inflamação. 2) A AMPK no núcleo ventromedial do hipotálamo, principalmente a isoforma alfa 1 ativa a termogênese aumentando a produção de calor na qual converte tecido adiposo branco em bege. Além disso, o uso do antagonista ?3 adrenérgico ou a ativação da AMPK foram capazes de atenuar a produção de calor melhorando a caquexia induzida pelo câncer. 3) Roedores com câncer possuem a via do IKK/mTOR ativada no núcleo arqueado do hipotálamo proporcionando anorexia e caquexia. Por outro lado, o bloqueio da S6K com adenovírus foi capaz de melhorar a anorexia. Portanto, esses achados permitem concluir que o hipotálamo funciona como um centro regulador da anorexia e caquexia induzida pelo câncer, abrindo novos horizontes para o tratamento do câncer / Abstract: The theory of diseases generated by inflammatory cytokine brought over the years evidence that the organism may produce cytokine with beneficial and deleterious responses. Nowadays, it is clear that the inflammation is a key mechanism in cancer pathophysiology. Interestingly, several studies suggest that hypothalamic AMPK and mTOR, important molecules in the energy balance control also is responsible for modulation of both inflammation and anorexia. The studies presented herein observed that: 1) Inhibition of hypothalamic AMPK leads to weight loss and central and systemic inflammation which potentiates the tumor growth. However, AMPK activation with AICAR, salicylate and vector viral might reverse the cancer-mediated anorexia. Nevertheless, benefic effects of AICAR are blunted with a combination of cholinergic antagonists, suggesting that ventromedial of hypothalamus (VMH)-specific AMPK action is responsible for the anorexia and inflammation control. 2) VMH-specific AMPK, particularly the isoform alpha 1 activates thermogenesis increasing heat production which switches the white adipose tissue in beige. Furthermore, ?3 adrenergic antagonist and AMPK activation were able to attenuate the heal generation, block the "browning of WAT" and improve the cancer cachexia. 3) Cancer rats have activated IKK/mTOR pathway in arcuate nucleus (ARC) of the hypothalamus. In contrast, neutralization of S6K through adenovirus was able to improve anorexia. Therefore, our data show evidences that the hypothalamus a key center that integrates a number of mechanisms triggered by cancer-induced anorexia and -cachexia, opening new horizons for the treatment of cancer / Doutorado / Fisiopatologia Médica / Doutor em Ciências

Orientador: Maria Cristina Cintra Gomes Marcondes / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-26T13:25:51Z (GMT). No. of bitstreams: 1 Cruz_BreadLeandroGomesda_D.pdf: 1846989 bytes, checksum: 30a328ba2d64a0e66c6bb74d4c81d492 (MD5) Previous issue date: 2014 / Resumo: O câncer é uma das principais causas de morte no mundo e o quadro de caquexia provocado por alguns tipos de tumor é um dos grandes responsáveis por isso. A caquexia instaurada em pacientes com câncer, sendo mais prevalente nos tumores gastrointestinal, pulmonar, pancreático e mamário, é caracterizada, dentre outros processos, pela perda involuntária de peso, devido a constante espoliação sobre a massa magra corporal. Estudos que tenham como objetivo a manutenção da massa magra em organismos portadores de tumor caquético são importantes para contribuir com a redução de óbitos e preservar a qualidade de vida das pessoas com câncer. Nos últimos anos, a leucina tem mostrado ser eficaz na manutenção da massa magra corpórea através do estímulo de síntese protéica muscular e inibição da degradação de proteína, principalmente da massa magra corpórea. Logo, entender como a presença da leucina estimula a síntese protéica e atua de forma protetora em organismo no estado caquético tem se mostrado uma necessidade crescente. Desse modo, a proposta deste trabalho foi avaliar, ao longo do tempo, os efeitos de dieta rica em leucina sobre a sinalização de síntese e degradação protéica, envolvendo o complexo mTOR em músculos de ratos portadores do carcinossarcoma de Walker 256. Os animais foram distribuídos em grupos de acordo com a inoculação tumoral e/ou esquema nutricional com dieta rica em leucina, sendo sacrificados em três momentos diferentes do desenvolvimento tumoral (7º, 14º e 21º dias após a implantação do tumor). No músculo gastrocnêmio foram analisadas as proteínas-chave da via mTOR, como RAG A GTPase, ERK/MAP4K3, PKB/Akt, mTOR, p70S6K1, Jnk, IRS-1, STAT3, e STAT6 e, tambem, foram avaliadas as proteínas de degradação protéica pertencentes ao sistema ubiquitina-proteossomo (11S, 19S e 20S) e citocinas IL-4, IL-6, IL-10, TNF? e INF?. Os resultados mostram que o desenvolvimento tumoral reduziu a ativação de RAG-A, associada com queda de IRS-1, aumento da PKB/Akt e Erk/MAP4K3 no 21º dia e manutenção de p70S6K1; também houve aumento dos níveis de STAT-3 e STAT-6 em ratos portadores de tumor. Entretanto, a presença de leucina na dieta modulou etapas chave da via mTOR pelo desencadeamento da ativação aumentada de RAG-A e mTOR junto com a manutenção dos níveis de JNK, STAT-3 e STAT-6 no músculo durante o desenvolvimento do tumor de Walker no organismo caquético. A análise da sinalização para degradação protéica mostrou que o crescimento tumoral promoveu, simultaneamente, diminuição de proteína muscular, acentuado aumento de citocinas pró-inflamatórias (TNF?, IL-6 e IFN?) e aumento progressivo das subunidades proteossômicas (19S e 20S), sendo que a suplementação com leucina atenuou essa ativação. Os resultados obtidos apoiam o efeito benéfico do uso de leucina e esclarece as vias metabólicas utilizadas por este aminoácido, contribuindo para melhor compreensão da ação in vivo desse aminoácido sobre a caquexia / Abstract: Cancer is one of the most important causes of death worldwide and the process of cachexia caused by some types of tumour is largely responsible for this. Cancer-cachexia state established in these patients is characterized, among other processes, by involuntary loss of weight due to constant spoliation of lean body mass. Many studies aim to focus in maintenance of lean body mass in cachectic tumour-bearing host, contributing to the reduction of deaths and improving the quality of life of cancer patients. In recent years, leucine has been shown to be effective in maintaining lean body mass by stimulating muscle protein synthesis and inhibiting the proteolysis. Therefore, there are increased needs in understanding how the presence of leucine stimulates protein synthesis and acts protectively in the cachectic state. The aim of this work is to evaluate the effects of leucine-rich diet in a time-course model on signalling protein synthesis and degradation involving mTOR complex in muscles of Walker 256 carcinoma-bearing rats. Animals were divided into experimental groups based on the tumour inoculation and/or fed a nutritional supplementation diet rich in leucine. Animals were sacrificed at three different times depending on the tumour development (7, 14 and 21 days after tumour implantation), and the gastrocnemius muscles were analysed as mTOR pathway and ubiquitin-proteasome via. The results showed that the tumour development has reduced the activation of RAG-A, associated with a decrease of IRS-1, increased PKB / Akt and Erk / MAP4K3 at day 21 and maintaining p70S6K1, there has also been increasing levels of STAT-3 and STAT-6 in tumour-bearing rats. Meanwhile, the presence of leucine in the diet modulated the key steps of the mTOR pathway for triggering the increased RAG-A and mTOR activation along with the maintenance of levels of JNK, STAT-3 and STAT-6 in the muscle during tumour development in cachectic host. The gastrocnemius muscle signalling of protein degradation indicated by the ubiquitin-proteasome subunits (11S, 19S and 20S) and pro- and anti-inflammatory cytokines were marked increase of pro-inflammatory cytokines (TNF?, IL-6 and IFN?) and a progressive increase in the proteasome subunits (19S and 20S) associated with simultaneously decreased muscle protein. The supplementation with leucine attenuated these parameters, suggesting the beneficial effect of the use of leucine and clarifies the metabolic pathways used by this amino acid, contributing to better understanding of the in vivo action of this amino acid on cachexia / Doutorado / Fisiologia / Doutor em Biologia Funcional e Molecular

A redução do consumo de alimentos é freqüente durante a descompensação da insuficiência cardíaca, quando há um aumento do gasto energético basal. Os triglicérides de cadeia média, utilizados como suplementação energética, aumentam a densidade calórica dos alimentos, contribuindo para o metabolismo energético dos pacientes com insuficiência cardíaca. O objetivo foi avaliar o efeito da suplementação de triglicérides de cadeia média sobre o quoeficiente respiratório, na insuficiência cardíaca congestiva e na baixa ingestão alimentar. Foi realizado um estudo randomizado aberto com 45 pacientes de 18 a 70 anos com insuficiência cardíaca congestiva descompensada, fração de ejeção < 0,45, sem drogas vasoativas, dieta oral, IMC < 25kg/m2 para adultos e < 27 kg/m2 para idosos. Foram alocados aleatoriamente para grupo com suplementação de TCM e grupo controle. Os grupos realizaram duas medidas de VCO2 e VO2, por calorimetria indireta. O QR foi avaliado pela análise de variância com medidas repetidas. Foi considerado significante P < 0,05. 75% dos pacientes foram identificados em eutrofia pelo IMC, porém destes, 67% foram diagnosticados com desnutrição calórica e 65% com desnutrição protéico calórica quando analisados e classificados os indicadores de dobras cutâneas. A proporção de lipídeos aumentou de 9,5% para 57% das recomendações com 236,7 ± 95,0 kcal/d do triglicérides de cadeia média (P <0,001). A ingestão de calorias aumentou de 1966,3 ± 643,3 kcal /d para 2202,7 ± 708,4 kcal /d no grupo intervenção e manteve 1960,7 ± 702,6 kcal /d no grupo controle. Não houve variação significativa quoeficiente respiratório (grupo triglicérides de cadeia média +0,4%; grupo controle: +2,5%, P = 0,458). Quatro pacientes apresentaram efeitos adversos ao suplemento, no entanto, sem necessidade de suspensão. O triglicéride de cadeia média não reduziu o quoeficiente respiratório, no entanto melhorou a proporção de carboidratos e lipídios, contribuindo para a melhora do aproveitamento energético. / Food intake reduction is frequent during decompensation of heart failure, when basal energy expenditure increases. In addition, medium chain triglycerides are used as energy supplementation increases caloric density of food, contributing to energy metabolism of patients with heart failure. The objective was to evaluate the effect of supplementation of medium chain triglycerides on the respiratory coefficient in congestive heart failure and low food intake. We conducted a randomized open label study with 45 patients from 18 to 70 years old with decompensated congestive heart failure, ejection fraction < 0,45, without intravenous inotropic drugs, oral diet and body mass index < 25 kg/m2 for adults and <27 kg/m2 for the elderly Patients were randomly allocated to supplementation with medium chain triglycerides or control group. They were submitted to two measurements of VCO2 and VO2 by indirect calorimetry. Analysis of variance with repeated measures analyzes respiratory coefficient change and two-sided. P< 0,05 was significant. 75% of patients were identified in eutrophic by body mass index, but these, 67% were diagnosed with calorie malnutrition and 65% with protein calorie malnutrition when analyzed and classified by skinfolds measures. Adequate proportion of carbohydrates and lipids increased from 9,5% to 57% of patients with 236,7 ± 95,0 kcal/d of medium chain triglycerides (P<0,001). Caloric intake increased from 1966,3 ± 643,3 kcal/d to 2202,7 ± 708,4 kcal/d in the medium chain triglycerides group and remained 1960,7 ± 702,6 kcal/d in control group. There was not a significant respiratory coefficient variation (medium chain triglycerides group +0,4%; control group: +2,5%; P=0,458). Four patients presented adverse effects with medium chain triglycerides; however, without requirement of withdrawal. Medium chain triglycerides did not reduce respiratory coefficient, however they improved carbohydrates and lipids proportion, contributing to improvement of energy utilization.

Cancer mortality is the second leading cause of death in the United States. It is estimated that 90% of these are attributed to stage IV metastatic disease, in which tumor cells have disseminated from the primary tumor to form clinically relevant macroscopic metastatic colonies in distant organs. While advances in early screening protocols, surgical intervention and treatment with chemotherapy, radiation therapy, immunotherapies, and targeted therapies have improved the management of primary tumors in early stage cancer patients; cancers that have progressed to metastatic disease are often resistant to these strategies and generally represent a terminal illness. Furthermore, even aggressive treatment of some cancers, such as triple-negative breast cancer, can often leave behind significant residual cancer burden that can spontaneously relapse and culminate in metastatic disease, even years after initial treatments. Until advances throughout the last century, metastasis-associated cancer mortality was thought to be largely attributed to local complications due to widespread tumor burden, such as the physical crushing of vital organs and damage to blood circulation, neuron circuitry, and the gastrointestinal tract. And while these are often causes metastasis-associated mortality, studies have revealed that cancer metastasis is a systemic illness that dysregulates the host’s metabolism and immune system. It is now well known that tumor cells themselves or through signaling with non-tumor cells – can release a milieu of soluble factors, exosomes, and metabolites that can systemically alter host metabolism, physiology, and immune regulation to promote metastasis and compromise natural homeostasis. These systemic alterations often culminate in a lethal condition known as cachexia, which is defined as: “a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reserved by conventional nutritional support and leads to progressive functional impairment”. Cancer-associated cachexia develops in about 80% of metastatic cancer patients, depending on cancer type, has no approved efficacious treatments, and is associated with 20% of all cancer-related deaths due to severe loss muscle mass and function. Here, we show that the aberrant muscle-cell upregulation of the metal ion importer, ZIP14, expression and concomitant increase in intramuscular zinc is associated with the development of cachexia in Pan02 and FC1242 experimental metastasis models of pancreatic adenocarcinoma and a Bard1-deficient model of BRCA-like triple-negative breast cancer. Furthermore, we show that ZIP14 expression is highly upregulated human advanced pancreatic adenocarcinoma patients. These findings are consistent with our previous studies that show the ZIP14-zinc axis mediates the development of cachexia in metastatic models of breast, lung, and colon cancer and suggest that inhibition of ZIP14 function or zinc chelation strategies may provide a potential therapeutic option for the prevention or treatment of metastasis-induced cachexia. In addition to systemic metabolic dysregulation, metastatic cancers also locally or systemically dysregulate immune responses and immune cell populations to promote tumor growth and help facilitate metastasis. As the tumor progresses and metastasizes, tumor cell- or tumor stroma-derived factors polarize many myeloid and lymphocyte cell populations into tumor-promoting subsets that can suppress anti-tumor immune response through the production of immunosuppressive cytokines or expression of co-inhibitory molecules, remodel the extracellular matrix, induce angiogenesis, and promote the survival, proliferation, and motility of tumor cells. These tumor-associated factors can also dysregulate the hematopoiesis of immune cells, resulting in a systemic alteration of immune cell populations, such as peripheral expansion of immunosuppressive, immature myeloid-derived suppressor cells or T-regulatory cells. While the functional roles and subsets of tumor-infiltrating myeloid and T lymphocytes have been extensively studied, the role and function of tumor-infiltrating B lymphocytes are less defined, especially in the metastatic context. Here, we show that a population of B220+ B cells is recruited to the invasive margin of lung metastases in triple-negative breast cancer patients and 4T1 and LM3 metastatic mouse models of triple-negative breast cancer. Furthermore, B220+ B cells isolated from the metastatic lungs of the 4T1 and LM3 triple-negative breast cancer models were found to enhance the invasion of lung metastasis-derived organoids in 3-dimensional co-culture and promote the migration of triple-negative breast cancer cell lines. We confirmed that 4T1 B cell-deficient mouse models exhibit impaired formation of lung metastases and a concomitant reduction in the proportion of cytokeratin-14+ invasive leader tumor cells and p-mTOR+ tumor cells per lung metastasis, suggesting that the B cell-associated invasion-promoting mechanism is mediated in part by p-mTOR. We further show that the lung metastases of triple-negative breast cancer patients with high tumor-infiltrating B cell density exhibit increased p-mTOR expression compared to patients with low tumor-infiltrating B cell density. Taken together, our findings provide evidence of a tumor invasion-promoting function for metastasis-infiltrating B cells in metastatic triple-negative breast cancer and suggest that further elucidation of the metastasis-infiltrating B cell phenotype and the role of p-mTOR in the tumor cell-B cell invasion-promoting mechanism may reveal promising targets for the treatment of triple-negative breast cancer patients.