Natural killer (NK) cells are lymphocytes of the innate immune response characterized by their role in the destruction of tumor cells. Activation of NK cells depend on a fine balance between activating and inhibitory signals mediated by different receptors. In recent years, a family of paired receptors that interact with ligands of the Nectin/Nectin-like (Necl) family has attracted great interest. Two of these ligands, Necl-5 (usually termed CD155 or PVR) and Nectin-2 (CD112), frequently expressed on different types of tumor cells, are recognized by a group of receptors expressed on T and NK cells that exert opposite functions after interacting with their ligands. These receptors include DNAM-1 (CD226), TIGIT, TACTILE (CD96) and the recently described PVRIG. Whereas activation through DNAM-1 after recognition of CD155 or CD112 enhances NK cell-mediated cytotoxicity against a wide range of tumor cells, TIGIT recognition of these ligands exerts an inhibitory effect on NK cells by diminishing IFN-γ production, as well as NK cell-mediated cytotoxicity. PVRIG has also been identified as an inhibitory receptor that recognizes CD112 but not CD155. However, little is known about the role of TACTILE as modulator of immune responses in humans. TACTILE control of tumor growth and metastases has been reported in murine models, and it has been suggested that it negatively regulates the anti-tumor functions mediated by DNAM-1. In NK cells from patients with solid cancer and leukemia, it has been observed a decreased expression of DNAM-1 that may shift the balance in favor to the inhibitory receptors TIGIT or PVRIG, further contributing to the diminished NK cell-mediated cytotoxic capacity observed in these patients. Analysis of DNAM-1, TIGIT, TACTILE and PVRIG on human NK cells from solid cancer or leukemia patients will clarify the role of these receptors in cancer surveillance. Overall, it can be speculated that in cancer patients the TIGIT/PVRIG pathways are upregulated and represent novel targets for checkpoint blockade immunotherapy.

Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56− T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56− T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1−TIGIT+TACTILE+ NK cells and DNAM-1− TIGIT+TACTILE+ CD56− T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.

Elastography is a sonographic technique that provides a noninvasive evaluation of the stiffness of a lesion. The objective of this work was to evaluate the accuracy of strain elastography, the most accessible modality in clinical practice, to discriminate between different histological types of malignant mammary neoplasms in the canine species, which can provide complementary information in real time to the diagnosis and thus help in the choice of surgical technique. A total of 34 females with 56 mammary carcinomas were selected and classified into three histological groups according to their aggressiveness. The histological and elastographic characteristics of these malignant tumors were analyzed and compared to evaluate the diagnostic accuracy of strain elastography. Visual score presented a sensitivity of 88.0%, specificity of 58.1%, and accuracy of 71.43% in distinguishing the most aggressive group of carcinomas. The strain ratio had a sensitivity of 84.0%, specificity of 61.1%, and accuracy of 69.64%. On the other hand, intratumoral strain ratio obtained a sensitivity of 71.40% and specificity of 61.90% when intratumoral fibrosis was taken as reference, with an accuracy of 66.07%. Similarly, peritumoral strain ratio was also positively related to fibrosis in the periphery of lesions (p ≤ 0.001), with a sensitivity of 93.80%, specificity of 77.50% and an accuracy of 92.87%. In conclusion, accuracy of this elastographic modality can be a useful method to differentiate more aggressive histological types. Therefore, it represents an additional diagnostic technique useful in the daily clinic thanks to the short time required for the examination, which allows real-time visualization and immediate interpretation of the results.

Primary tracheal neoplasia is uncommon in domestic animals and humans, and most reported tracheal tumours are malignant. To the authors’ knowledge, this case represents the third confirmed case of tracheal leiomyoma reported in dogs. In human medicine, tracheal leiomyomas have also only been reported sporadically and account for approximately 1% of tracheal tumours. A 12-year-old spayed female Pit Bull was presented as an emergency because of an acute worsening of recurrent respiratory signs that were refractory to medical treatment. On initial evaluation, reduced mobility of both arytenoid cartilages was observed, and left arytenoid lateralisation was therefore performed. However, four days after the procedure, the dog continued to experience severe episodes of respiratory distress requiring orotracheal intubation. Subsequent bronchoscopy revealed an intraluminal tracheal mass occupying approximately 90% of the airway lumen. Because of this obstruction, an emergency temporary tracheostomy was performed caudal to the mass. Once the dog had been clinically stabilised, computed tomography was performed for surgical planning. Surgical treatment consisted of segmental tracheal resection and end-to-end anastomosis, with removal of a segment corresponding to 24% of the total tracheal length. Histopathological examination confirmed the diagnosis of tracheal leiomyoma. Complete surgical excision was achieved, supporting a favourable prognosis.

Primary tracheal neoplasia is uncommon in domestic animals and humans, and most reported tracheal tumors are malignant. To the authors’ knowledge, this case represents the third confirmed tracheal leiomyoma reported in dogs. Similarly, in human medicine, tracheal leiomyomas have only been reported sporadically and account for approximately 1% of tracheal tumors. A 12-year-old spayed female Pitbull was presented as an emergency because of worsening recurrent respiratory signs that were refractory to medical treatment. On initial evaluation, reduced mobility of both arytenoid cartilages was observed, and left arytenoid lateralization was therefore performed. However, the patient continued to experience severe episodes of respiratory distress requiring orotracheal intubation. Subsequent bronchoscopy revealed an intraluminal tracheal mass partially obstructing the airway lumen. Because of this obstruction, an emergency temporary tracheostomy was performed caudal to the mass. Once the patient was clinically stabilized, computed tomography was performed to complete surgical planning. Surgical treatment consisted of segmental tracheal resection and end-to-end anastomosis, with removal of 24% of the total tracheal length. Histopathological examination confirmed the diagnosis of tracheal leiomyoma. Complete surgical excision was achieved, supporting a favorable prognosis.