The biological aspects of infancy within late Upper Palaeolithic populations and the role of southern refugia at the end of the Last Glacial Maximum are not yet fully understood. This study presents a multidisciplinary, high temporal resolution investigation of an Upper Palaeolithic infant from Grotta delle Mura (Apulia, southern Italy) combining palaeogenomics, dental palaeohistology, spatially-resolved geochemical analyses, direct radiocarbon dating, and traditional anthropological studies. The skeletal remains of the infant – Le Mura 1 – were directly dated to 17,320-16,910 cal BP. The results portray a biological history of the infant’s development, early life, health and death (estimated at ~72 weeks). They identify, several phenotypic traits and a potential congenital disease in the infant, the mother’s low mobility during gestation, and a high level of endogamy. Furthermore, the genomic data indicates an early spread of the Villabruna-like components along the Italian peninsula, confirming a population turnover around the time of the Last Glacial Maximum, and highlighting a general reduction in genetic variability from northern to southern Italy. Overall, Le Mura 1 contributes to our better understanding of the early stages of life and the genetic puzzle in the Italian peninsula at the end of the Last Glacial Maximum.

Ancient human remains have the potential to explain a great deal about the prehistory of humankind. Due to recent technological and bioinformatics advances, their study, at the palaeogenomic level, can provide important information about population dynamics, culture changes, and the lifestyles of our ancestors. In this study, mitochondrial and nuclear genome data obtained from human bone remains associated with the Neolithic Globular Amphorae culture, which were recovered in the Megalithic barrow of Kierzkowo (Poland), were reanalysed to gain insight into the social organisation and use of the archaeological site and to provide information at the individual level. We were able to successfully estimate the minimum number of individuals, sex, kin relationships, and phenotypic traits of the buried individuals, despite the low level of preservation of the bone samples and the intricate taphonomic conditions. In addition, the evaluation of damage patterns allowed us to highlight the presence of “intruders”—that is, of more recent skeletal remains that did not belong to the original burial. Due to its characteristics, the study of the Kierzkowo barrow represented a challenge for the reconstruction of the biological profile of the human community who exploited it and an excellent example of the contribution that ancient genomic analysis can provide to archaeological reconstruction.

While microsatellite-instable (MSI) colorectal cancers (CRC), reflecting mismatch repair deficiency, often respond to immune checkpoint inhibitors, microsatellite-stable (MSS) tumors remain largely resistant. This disparity is typically attributed to differences in neoantigen load. However, whether antigen-independent mechanisms contribute to immune evasion in MSS-CRC remains unclear. To address this, we engineered a model in which MSI- and MSS-CRC cells express identical levels of a defined antigen recognized by TCR-engineered T cells. Despite equivalent antigen presentation, MSS tumors exhibited impaired T-cell activation, reduced cytotoxicity, and resistance to killing. We linked this immune evasion to the MSS tumor secretome, which suppressed immune responses even in immunogenic MSI cells by impairing immune synapse formation. Surfaceome profiling by mass spectrometry identified glycosylation-dependent alterations that impair immune recognition. Our findings demonstrate that MSS-CRC evades immune attack via intrinsic secretome-driven mechanisms, independent of antigenicity. Targeting glycosylation-linked suppressive pathways may restore T-cell responsiveness and improve immunotherapy efficacy in MSS-CRC.

Main clinicopathologic features of the cohort of patients with colorectal cancer.

Statistically significant membrane proteins differentially expressed in MSI_05 organoids exposed to MSI- vs MSS-conditioned media.