SWI/SNF complexes are a conserved eukaryotic family of chromatin remodelling activities. In mammalian cells, this family can be divided simplistically into three categories: BAF (BRG1/BRM Associated Factors), PBAF (Polybromo-associated BAF), and GBAF (GLTSCR1/1L-associated BAF; also called ncBAF). BAF, PBAF and GBAF share some core subunits (Table 1) and are defined by complex-specific subunits [1]. Of note, many subunits have multiple isoforms and paralogues. Moreover, each complex will have one of two catalytic subunits; SMARCA4 (also called BRG1) or SMARCA2 (also called BRM). Each category of SWI/SNF complex (BAF, PBAF and GBAF) therefore has many possible variations, and a full understanding of the specific functions of each is not yet known.

The SWI/SNF complexes regulate gene expression through remodelling activity at promoter and enhancer elements [2]. Misregulation of gene expression in cells with SWI/SNF deficiency can contribute to changes in genome stability, but SWI/SNF complexes also play a transcription-independent role in maintaining genome stability (described in more detail below). For example, SWI/SNF complexes are recruited to sites of DNA double strand breaks and promote their timely and accurate repair (for review, see [1]).

It has become increasingly apparent that genome instability can feed into both innate and adaptive immune responses (for recent reviews on this topic, see Zhou and Mouw, Ha et al., Uchihara and Shibata, and Zierhut, this issue). Genome instability events, such as mitotic progression with unrepaired DNA damage, that lead to the generation of cytosolic DNA fragments can activate the cGAS/STING pathway, triggering a type I interferon response. Furthermore, defective mismatch repair or misrepair of DNA breaks that culminate in elevated tumour mutational burden (TMB) can result in neoantigen formation. Moreover, DNA damage leads to enhanced HLA class I presentation [3]. Each of these responses has the potential to turn an immunologically ‘cold’ tumour into a ‘hot’ one, which in turn can improve the response to immune checkpoint inhibitor (ICI) therapy [4].

Interestingly, SWI/SNF alterations have been identified as prognostic indicators for ICI therapy response. Specifically, loss of function mutations in PBRM1 subunit correlate with improved response to ICI therapy [5], [6], [7], [8], [9]. In addition, mutations in other subunits, including ARID1A and ARID2, also showed potential prognostic value [10], [11]. However, relationships were not apparent in all tissue types or with all SWI/SNF subunits, and in some cases, no positive association between SWI/SNF alterations and response to ICI therapy was apparent (for example, [12], [13], [14], [15]). Understanding how SWI/SNF deficiency impacts on immune responses, and consequently how SWI/SNF deficiency might influence ICI therapy response, is still an open and clinically important question.

There is evidence that SWI/SNF complexes can regulate expression of genes involved in immune signalling (for example, [9], [16], [17]), and therefore altered SWI/SNF activity could influence ICI therapy response through the resulting changes in immune gene expression. However, here, we focus on SWI/SNF activities involved in genome maintenance that might influence immune responses indirectly. In some cases, there is direct evidence of a relationship between genome instability caused by SWI/SNF deficiency and immune signalling. In addition, we highlight areas where the impact of specific SWI/SNF-dependent DNA damage responses on immune responses is predicted but has yet to be tested. Given the prevalence of SWI/SNF dysregulation in cancer, understanding these relationships in more detail will be helpful when considering therapeutic approaches.