Alterations of the immune system could seriously impair the ability to combat infections during future long-duration space missions. However, little is known about the effects of spaceflight on the B-cell compartment. Given the limited access to astronaut samples, we addressed this question using blood samples collected from 20 healthy male volunteers subjected to long-duration bed rest, an Earth-based analog of spaceflight. Hematopoietic progenitors, white blood cells, total lymphocytes and B-cells, four B-cell subsets, immunoglobulin isotypes, six cytokines involved in inflammation, cortisone and cortisol were quantified at five time points. Tibia microarchitecture was also studied. Moreover, we investigated the efficiency of antioxidant supplementation with a cocktail including polyphenols, omega 3, vitamin E and selenium. Our results show that circulating hematopoietic progenitors, white blood cells, total lymphocytes and B-cells, and B-cell subsets were not affected by bed rest. Cytokine quantification suggested a lower systemic inflammatory status, supported by an increase in serum cortisone, during bed rest. These data confirm the in vivo hormonal dysregulation of immunity observed in astronauts and show that bed rest does not alter B-cell homeostasis. This lack of an impact of long-term bed rest on B-cell homeostasis can, at least partially, be explained by limited bone remodeling. None of the evaluated parameters were affected by the administration of the antioxidant supplement. The non-effectiveness of the supplement may be because the diet provided to the non-supplemented and supplemented volunteers already contained sufficient antioxidants. Given the limitations of this model, further studies will be required to determine whether B-cell homeostasis is affected, especially during future deep-space exploration missions that will be of unprecedented durations.

Using rotors to expose animals to different levels of hypergravity is an efficient means of understanding how altered gravity affects physiological functions, interactions between physiological systems and animal development. Furthermore, rotors can be used to prepare space experiments, e.g., conducting hypergravity experiments to demonstrate the feasibility of a study before its implementation and to complement inflight experiments by comparing the effects of micro- and hypergravity. In this paper, we present a new platform called the Gravitational Experimental Platform for Animal Models (GEPAM), which has been part of European Space Agency (ESA)’s portfolio of ground-based facilities since 2020, to study the effects of altered gravity on aquatic animal models (amphibian embryos/tadpoles) and mice. This platform comprises rotors for hypergravity exposure (three aquatic rotors and one rodent rotor) and models to simulate microgravity (cages for mouse hindlimb unloading and a random positioning machine (RPM)). Four species of amphibians can be used at present. All murine strains can be used and are maintained in a specific pathogen-free area. This platform is surrounded by numerous facilities for sample preparation and analysis using state-of-the-art techniques. Finally, we illustrate how GEPAM can contribute to the understanding of molecular and cellular mechanisms and the identification of countermeasures.

The identification of safe and easily-determined-inflight biomarkers to monitor the immune system of astronauts is mandatory to ensure their well-being and the success of the missions. In this report, we evaluated the relevance of two biomarkers whose determination could be easily implemented in a spacecraft in the near future by using bedridden volunteers as a ground-based model of the microgravity of spaceflight. Our data confirm the relevance of the neutrophil to lymphocyte ratio (NLR) and suggest platelet to lymphocyte ratio (PLR) monitoring to assess long-lasting immune diseases. We recommend coupling these ratios to other biomarkers, such as the quantification of cytokines and viral load measurements, to efficiently detect immune dysfunction, determine when countermeasures should be applied to promote immune recovery, prevent the development of disease, and track responses to treatment.

Background: BIA-ALCL is a rare subtype of T cell lymphomas associated with textured breast implants which has recently been recognized. The pathogenesis of this entity remains elusive even if mutations in the JAK/STAT pathway have been identified. Little is known about the causes, prognostic factors of this disease, and treatment outcome. Methods: since 2016, a WebEx national multidisciplinary meeting has been implemented by the French Cancer Agency in order to better define therapeutic strategies for newly diagnosed cases after histologic confirmation. In the same time, BIA-ALCL registry was funded by LYSA in order to collect ambispectively, in France and Belgium, patient clinical data including reasons for breast implantation (breast augmentation, reconstruction), implant manufacturer, treatments and outcome. A biological program aiming molecular characterization of this T-cell lymphoma subtype has been set in coordination with the registry. Results: Fifty-eight patients (pts) have been analyzed so far among the 88 (67 in France and 21 in Belgium) identified from 2009 to 2019. Median age was 58 years (range 29-82) at diagnosis. In 29 out of the 58 pts (50%) the first implant followed a mastectomy for breast cancer. In this analysis, only implants in the breast(s) where the lymphoma occurred have been considered. Four pts (6.9%) had bilateral lymphoma and 54 pts had unilateral lymphoma (50% left side and 50% right side), 25 pts were implanted once (43.1%), 24 twice (41.4%) and 9 pts (15.5%) 3 times or more. The median delay between first implant and BIA-ALCL diagnosis was 11.9 years (range 4.1-37), and median delay from last implant to diagnosis was 6.5 years (range 0.2-25.4). The two clinical presentations i.e. seroma (n = 43, 74.1%) and breast tumor mass with or without seroma (n = 12, 20.7%) were most often correlated with the two distinct histological subtypes (in situ /mixed (n=41) or infiltrative (n=17). Three pts were diagnosed without any mass or seroma (1 lymph node involvement, 2 in the context of systematic implant removal). The majority of pts were stage I-II (n=45, 77.6%), and 13 (22.4%) pts were stage IV. One hundred and five implants have been used on lymphoma associated breast for these 58 patients. Considering available information regarding the type of implants, almost all patients had at least one silicone-filled (n=51) and at least one textured implant (n=49) with Biocell texturation (n=40, 69%). No patient had only smooth implant. Implant removal with total capsulectomy was performed in 49 patients and 17 underwent chemotherapy based mostly on CHOP or CHOP-like chemotherapy regimens (n=12) and brentuximab vedotin CHP (n=3). After 21 months of median follow-up, 52 pts are alive and free of evolutive disease and one was lost to follow up. Five pts have died, either from lymphoma progression alone (n=2), or associated with concomitant active breast cancer (n=2) and one due to another disease. All had an infiltrative histology, and the 2 patients who died from lymphoma were stage IV. All but one received systemic chemotherapy and one received palliative care only due to concomitant active breast cancer. One of these patients early relapsed after a first complete remission. After the BIA-ALCL diagnosis, breast reconstruction was performed in in 23 pts (39.7%), 17 with a new implant, lipofilling in 4 pts, with a flap in 4 pts, and one benefit from combined approaches. Whole exome sequencing and/or targeted deep sequencing was performed in 29 of these patients. Recurrent mutation of epigenetic modifiers were seen in 22 pts (76%) involving notably KMT2C (28%), CM2D (14%) and CREBBP (14%). Eighteen pts (62%) showed mutations in at least one member of JAK STAT signaling pathway including STAT3 (38%) and JAK1(21%). Conclusions: We here confirm that in situ BIA-ALCLs have an indolent clinical course and remain in complete remission mainly after implant removal. Infiltrative histological subtype which have a more aggressive clinical course should be precisely identified at baseline. In our series, most BIA-ALCL cases were associated with macrotextured implants with Biocell texturation observed in 69% of the cases. The molecular characterization of these cases highlights the key role of the JAK/STAT pathway, and the importance of epigenomics. Such observation provide basis to develop novel targeted therapies for patients with aggressive disease. Disclosures Le Bras: Takeda: Research Funding; Pfizer: Other: Travel grant; Jansen: Other: Travel grant. Haioun:novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy; gilead: Consultancy; takeda: Consultancy; janssen cilag: Consultancy; amgen: Honoraria; servier: Honoraria. Bachy:Janssen Cilag: Honoraria; Janssen Cilag: Other: Travel, accomodation, Expense; Roche: Honoraria; Amgen: Honoraria; Roche: Consultancy; Gilead Science: Honoraria. Oberic:Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria. Tilly:Roche: Consultancy; roche: Membership on an entity's Board of Directors or advisory committees; servier: Honoraria; merck: Honoraria; Gilead: Honoraria; Janssen: Honoraria; BMS: Honoraria; Karyopharm: Consultancy; Astra-Zeneca: Consultancy; Celgene: Consultancy, Research Funding.

Spaceflight is an adverse environment characterized by a unique combination of stressors affecting almost all physiological systems, including the immune system. Indeed, several studies have shown that about 50% of the astronauts have faced immunological troubles. Here, we will review how spaceflight affects immune cell development, innate as well as adaptive immunity, required to ensure an efficient protection of the host, with a particular focus on T and B cells. Indeed, to better appreciate the risks associated to future long-duration space missions and to develop pharmacologic or nutritional countermeasures allowing immune system protection, it is mandatory to fully understand how these cell types are affected by space conditions. Finally, we will compare immune changes observed in astronauts with those encountered in the elderly, thereby illustrating the societal interest of space research.